What is the greater regional risk, when both Ebola and MERS have at least 40% fatality rate in the susceptible? although the desperately poverty-stricken in west Africa are far more vulnerable to ebola (from bat and common human transmission) than Saudis to MERS (from camel, and seldom human transmission).

5 September 2015: with the Hajj only a fortnight away, the fresh MERS outbreak in KSA continues its upsurge, with the past week 34 cases and 11 deaths ie still rising weekly rates. Compared to 16 cases and 7 deaths there in July, August had eight times more– 127 cases; and 42 deaths ie 33% mortality. Worse, the human outbreak has spread from Riyadh all over the country except on the coast. .

What is even more puzzling is that the KSA now plans to pay out over a $billion ie $133 300 compensation for each of the >1200 people who have died there of MERS . This is despite the fact that, as reported repeatedly on links below, their own scientists keep publicizing that residents there have severe vitamin D deficiency owing to the KSA culturally enforced sun exclusion ie coverup code especially for older adults. And that it costs no more than ~$5 a year for vitamin D3 for each person to take a harmless multidisease protective dose eg adults 50 000 iu every fortnight if not weekly ( as with any microbial after a loading therapeutic dose of eg 200 000 to 500 000iu if indicated ), with which we get excellent protection everywhere. Unlike their excellent doctors, KSA authorities dont publish a word of warning and prevention on their English websites about the deficiency of vits C & D well shown in their urban population.

26 August 2015 : while the MERS outbreak in S Korea terminated weeks ago at 184 cases and 29 deaths- ie 16% mortality, with no cases reported anywhere else outside Saudi Arabia in the world, where there were only 129 cases and 32deaths; the latest score from Riyadh KSA is 1171 cases and 502 deaths ie 43 cases and 15 deaths the past week.

Yet a new statement from the KSA MOH this week makes no mention of the apparent chief risk factor for MERS in KSA – their observant citizens’ profound deficiency of the sunshine vitamin D3 that their sharia sun-excluding apparel promotes, and that their health professionals have stressed for years, and that is so easily corrected by lifesaving vitamin D3 supplement at negligible cost. Only prisoners denied any sunshine and supplements have as bad vitamin D deficiency.

25 Aug 2015just a month before the 2015 Hajj, Saudi Arabia has announced a fresh MERS epidemic this month – based exclusively in Riyadh: in July there were only 16 new cases with 7deaths (compared to June‘s 27/14) ie the rate fell to about 4 cases a week. But this August the rate has mushroomed twelve-fold since July, from 4 to 22/wk, to now ~48 cases alone the past week @ ~7/day – 72% men; ie already this month 105 cases, 31 deaths; ie the recent death-rate has strayed to 29%. . One of today’s 6 deaths was among the 8 new cases reported today. Almost all the cases lately have apparently been reported from one Riyadh hospital the King AbdulAziz center. so the reported totals from KSA are now 1165 cases and 498 deaths ie 43% deathrate; with critical cases/ deaths mostly in the elderly. .

So is more incidental MERS contamination being detected by wider surveillance of well contacts? One can speculate whether the recent spurt, and deathrate, in KSA are because of wider MERS surveillance of asymptomatic people; and the very old dying of usual causes? when finding of the virus may be coincidental, not pathogenic? Does symptomatic stable indicate anything more than a common febrile URTI? The figures on the KSA Govt website are radically different from those on the FluTrackers.com site.

And VITAMIN D DEFICIENCY THERE? a new paper in Med Hypotheses. 2015 Aug from KSA again highlights the Saudi scientific community plea not to ignore the disaster of epidemic and so easily and cheaply remediable vitamin deficiency there- at least 63% are moderate to severely vitamin D deficient: Nabi, Hobani ea Jazan University, KSA ask: Can we hypothesize a link?High prevalence of vitamin D deficiency and cancer in KSA populations: In spite of so much sunshine, about 83.6% of Saudis are deficient in the ‘sunshine vitamin’ D – 31.9% have severe, 32% have moderate and 19.7% have mild vitamin D deficiency (VDD). Females are more severely vitamin D deficient. Apart from the genetic anti-vitamin D factor- darker skin color – various manmade factors contributing to skin sunlight deficiency and thus likely to epidemic viruses (and also significantly shorter adult life expectancy compared to other opulent countries) include housing designs, religious practices, lifestyle choices- which in ultra-conservative-run KSA seem to be uniquely sun-exclusive, and rigorously enforced.

27 June Update while the outbreak has leveled off in KSA at 1039 cases with 460 deaths ie 44%, – only 8 cases but 7 deaths the past fortnight- the total in S Korea has mushroomed to 182 with 31 deaths ie mortality up to 17%. 19 June 2015 South Korea reported ‘its 24th death from the MERS virus and one new case, bringing to 166 the total number of confirmed cases since the first one was diagnosed on May 20′; with mortality now up to 13% . ‘The number of people in quarantine has fallen 12 percent from the previous day to 5,930. Currently, 112 patients are in hospital for treatment and 30 others have been cured and released.Thailandbecame the 27 th country (following S Korea and China) to be infected with the respiratory virus, took 4 Days To Confirm first MERS Case- a 75-year-old businessman from Oman, Leading To Worries About Deadly Disease’s Spread. ‘ India and Muslim countries gird themselves as risk escalates with Ramadan pilgrimage to the source- KSA Saudi Arabia- now in full swing.

As especially in Muslim countries, and China, and South Africa, and all darkskinned people who shun the sun- as do all who use sunblockers, prefer avoiding tanned wrinkled or darker skin or skin cancer- or those who work and live mostly indoors and with covered bodies, limbs and often faces- Low vitamin D in yet another sunny country-Thailand; Jnl Clin Translat Endocr March 2015 Siwamogsatham ea. Vitamin D deficiency and insufficiency is also common in Thailand ( latitude between 5°30′ N and 20°30′ N) where adequate UVB exposure is available all year round. Chailurkit et al. [12] conducted the largest-scale examination of vitamin D status in Thai population,reported a 50% prevalence rate of vitamin D insufficiency & deficiency , defined as serum 25(OH)D level < 30 ng/mL . Life style and environmental factors are the major factors that determine vitamin D status.. Thai women are at risk likely due to sunscreen usage and sun avoidant behavior to maintain a fair complexion. Living in urban areas and with less leisure time in the sunlight., ncreases the risk of vitamin D insufficiency due to increased pollution, which decreases the amount of UVB available for cutaneous vitamin D synthesis. Furthermore, in Thailand dairy products are not fortified with vitamin D and very few vitamin D-rich foods are part of the Thai diet. Thus, dietary intake of vitamin D in Thai people is generally low.

17June 2015 update: while a German who contracted MERS in the Middle East in February has now died of lung complications in Germany, KSA Saudi Arabia reported 17 cases and 8 deaths in the past two weeks, similar to the rates in May; totals now 1035 with 458 deaths. Wiki puts the world totals (26 countries including the Korean who visited China) at 1340 cases with ~530 ie 39% deaths .

But originating from a single visitor to KSA, South Korea has now recorded 162MERS cases- 6 cases a day since 20 May- and 20deaths ie 12%. There a survey- Hong ea in Int J Tuberc Lung Dis 2014 – reported “Association between vitamin D deficiency and tuberculosis in S Korea, with healthy controls having frank vit D deficiency ( mean 25OHvitD level 16 ng/ml) but 60% higher than in TB patients (mean 9.86ng/ml). The prevalence of severe vitamin D deficiency was higher in patients with TB (51.1%) than in controls ( P = 0.001). The median 25(OH)D level increased from 11.40 ng/ml (IQR 7.85-15.73) to 13.18 ng/ml after treatment completion (P = 0.037). Presence of TB and history of TB were independently associated with severe vitamin D deficiency.”

Yet as is not available in local South African RSA TB-HIV clinics with prevalent vitamin D deficiency, there is still no reported policy of vitamin D supplementation apparently reported from S Korea (or KSA, or RSA) , despite (as in KSA and RSA) a study there 2 years ago (from Jeong of Dept Paediatrics at CHA University, Seongnam SKorea 2013) “Factors affecting the vitamin D status in South Korean children” finding ” prevalence of vitamin D deficiency ((15-20 ng/mL) was 19.5%. Overall, the mean serum 25(OH)D levels was 22.9±9.9 ng/mL. They were the highest in them preschoolers (2-5 years, 24.4 ng/mL) and the lowest in the adolescents (11-16 years,15.9 ng/mL). In addition, they were significantly higher in summer as compared with winter. The prevalence of vitamin D insufficiency and deficiency was relatively higher in our series of children. It is imperative that the public policies be established to provide vitamin D supplementation for South Korean children.”

ONGOING GLOBAL DENIAL OF NEED FOR MICRONUTRIENT SUPPLEMENTS:It seems that national authorities from the Americas to Europe to Africa to the middle east to Asia, including the medical industry, continue to refuse to heed overwhelming evidence that vigorous micronutrient supplements are needed, available, lowcost, highly effective and safe to prevent and treat epidemics like HIV-TB, flu, MERS and Ebola – especially when vaccines and antiviral drugs are without benefit, and when vitamin D deficiency is universal in clothed indoor-studying- and -working peoples, especially the poor who cannot buy supplements by choice. . .

6 June 2015 update:After a quiet April, KSA is now suffering fresh jeopardy from acute midsummer flareup of MERS. But so is the world with outbreak of MERS in Korea and China, while thousands of refugees from tribal wars in the middle east and North and even South Africa cause more concern for spread of such plagues.

As the Middle East girds itself against mounting Islamic warfare in the region, after only a handful of MERS cases in April- 8 cases and 6 deaths- KSA has in May seen 33 cases with >50% fatality – 18 deaths; and already in June the case rate has doubled from April’s 1 a day to May – June’s 2 cases a day, giving cumulative totals there to 6 June of 1026 MERS cases and 450 deaths..

By contrast, in South Korea only 5 deaths (8% mortality) have been reported in 84 cases so far the past 16 days – including a Korean who got to China. That chillingly brings the outbreak firmly onto the Asian mainland. South Korea now passes theUAEas the second biggest outbreak country after the KSA- but like the UAE and elsewhere, a far lower deathrate, perhaps simply because of initial contact tracking, since the outbreak has been totally in hospitals.

It seems that Vitamin D deficiency may be as much the cause of MERS susceptibility in South Korea as in KSA? A 2008 Korean University survey shows that despite its temperate latitude of ~35degrees, and humidity, South Korea had widespread vitamin D deficiency even in its young people: Serum 25-hydroxyvitamin D [25(OH)D] levels and the prevalence of vitamin D insufficiency defined as serum 25(OH)D level of less than 20 ng/ml.Vitamin D insufficiency was found in 47.3% of males and 64.5% of females, whereas only 13.2% of male and 6.7% of female population had a serum 25(OH)D level of greater than 30 ng/ml. Vitamin D insufficiency was most prevalent in the age of 20-29, with a rate of 65.0% in males and 79.9% in females, and least prevalent in the age of 60-69 in males and 50-59 in females. Those who work usually indoors were more predisposed to vitamin D insufficiency. In the adult population, predictors for vitamin D insufficiency included young age groups, spring and winter seasons, living in an urban area, and indoor occupations. CONCLUSIONS:Vitamin D insufficiency is very common, and it is now a greater threat to the younger generation in Korea. Current recommendations for vitamin D intakes for Koreans are inadequate, especially for the youth. In 2012 they reported “We found that vitamin D insufficiency or deficiency is a very common health problem in Korean adolescents, particularly in girls, and that serum 25(OH)D levels are inversely associated with insulin resistance and lipid profiles. These results suggest that more time spent in outdoor activity for sunlight exposure and higher vitamin D intake may be needed in younger adolescents in South Korea”

Ina recent university study by Han Seok Choi on vit D deficiency in S Korea- perhaps the worst measured vit D deficient country in the world? – he refers to Autier ea in Lyon France in JCEM 2012– “The average increase in (in adult) serum25(OH)D was 0.78 ng/ml per microgram of vitamin D3 supplement (40IU ) per day”. ie the average ~20ng/ml vit D level in so many deficient adults will increase by only ~8ng/ml for every 400iu vit D in an average daily “RDA” multi-supplement; to raise their level to a more efficient 60ng/ml requires at least ~2000iu/day or 60 000iu per month; and if diseased, to raise to a more vigorous 90ng/ml requires at least ~3000iu/d . But as others have reported, higher dose oral vitamin D3 gives a less vigorous response eg 10ng/ml rise per 1000iu/day; eg my 25OHvit D level is about 90ng/ml on about 9000iu vit D3 supplement a day (half-life estimated 2 weeks to 2 months in Modulation of the Immune Response to Respiratory Viruses by Vitamin D) and plenty of fat eg an average egg, cheese and doublecream yoghurt etc daily ; with no rise in my corrected serum calcium, and no visible calcification on my xray chest or echocardiogram . .Autier eawrote “76 trials published from 1984 to 2011 included 6207 subjects tested supplement doses ranging from 5 to 250 μg/d ie 200 to 10 000iu/d(median, 20 μg/d). In the absence of concomitant use of calcium supplements, average increase in serum 25-hydroxyvitamin D concentrations was 0.78 ng/ml (1.95 nmol/liter) per microgram ie 40iu of vitamin D3 supplement per day. Compared to the vitamin D3, the vitamin D2 was associated with significantly lower increases (P = 0.03). Concomitant use of calcium supplementation and high 25-hydroxyvitamin D concentration at baseline was nonsignificantly associated with lower increases in 25-hydroxyvitamin D concentrations.

“Vitamin D Deficiency Around the World 2015 Even the Indian Medical Association recently organized continuing medical education to address the rise of vitamin D deficiency in their sun-soaked nation. Endocrinologist Dr. Sanjay Badada told Times of India:1 “Vitamin D deficiency is rapidly gaining epidemic proportions yet it is the most under-diagnosed and under-treated nutritional deficiency in the world. In our experience, 40 percent to 50 percent patients get diagnosed with Vitamin D deficiency as a part of their normal routine tests with no apparent symptoms. On the other hand, 80 percent to 90 percent of patients who come in with musculoskeletal complaints such as back pains, unexplained muscle pains, or general fatigue suffer from Vitamin D deficiency. Vitamin D was also discussed at the 2015 European Congress of Endocrinology. One talk2 addressed the “Mediterranean paradox,” as researchers have tried to understand why as many as 90 percent of pregnant mothers (and their newborns) in the sunny Mediterranean region are deficient in vitamin D. A systematic review looking at 15 studies concluded that predictors of low maternal vitamin D concentration included dark skin and sartorial habits—meaning the manner in which they dress, or in this case, being too covered up, preventing sun exposure on bare skin. Moreover, vitamin D supplementation was very low, and few pregnant women met the recommended daily intake (RDI) of calcium and vitamin D.”

12 April 2015 update: KSA has now reported 977 cases with 426 deaths ie 43% deathrate. Ignoring the past 12 days (2 cases, 4 deaths), the March rate was 1.9 cases per day with 49% deathrate; in Feb it was 3/day with only 42% deathrate. so while the reported caserate is down by a third, the fatality ie deathrate is up almost 20%. The Wiki MERS report is now a month out of date, with climbing deathrate.

Perhaps the lull in new MERS case detection/reporting is merely a result of that region (like the war-torn Central Africa – never mind the ebola epidemic-) being in the middle of an ethnic Muslim religious war – genocide- by fanatical jihadists on both more “liberal” Islamists and other religions. This increasingly threatens to overthrow the 20thC-European-created hereditary tribal governments of the desert/camel/oilfield region- KSA, Yemen, Jordan, the Gulf States etc, as happened in Egypt; not to speak of the power vacuum instability created in Iraq and Libya by more recent Western elimination of virtual dictators without ability to ensure democratic succession there any more than in Egypt, Afghanistan or Pakistan; and the oppressive dictatorships that prevail in Iran and Syria..

24 March 2015 KSA reports 964 cases and 419 deaths ie only 6cases and 3 deaths the past week. The Ebola outbreak meanwhile simmers down in W Africa in its anniversary week. .New reports from North America again highlight the importance of optimizing vigorous vitamin D3 dose and blood levels.

15 March 2015 MERS so far this March, in KSA already 37 cases , ie 17 a week, 21 deaths. This brings the reported case KSA total to 957 cases, 416 deaths; but deathrate the past 4 weeks to ~57% (the KSA website) . With the timelag in KSA reporting to international registries, Wiki reports that to 12 Mar there were only 402deaths /938 cases in KSA ie 43% deaths; but 1082 cases worldwide with 439 ie 37% deathrate in 24 countries- 118 cases with 28 deaths in the 8 middle east nations surrounding the KSA, giving a deathrate around but not in KSA of only 24%, and 3 deaths in 7 cases in their 3 African neighbouring countries; and 8 deaths in 22 cases in 12 distant countries ie 36% deathrate.

so while there have apparently been no new MERS cases outside KSA in their summer for months, the ongoing reported caserate in KSA is alarming with the deathrate having climbed to 55%. Obviously, to explain the apparent rising deathrate, detection and reporting of new MERS cases in KSA will likely be increasingly of only serious respiratory cases and their immediate contacts; and otherwise unexplained deaths; but the fact is that 10 MERS- associated deaths were again detected there the past week..

So while camels rather than bats are teeming with MERS virus and believed to be the main vactor to their human compatriots, it is instructive to to see a number of recent studies (1, 2, 3) in north African camels showing that they have vitamin D levels 10 to 40 times higher than Arabian citizens who import them en masse, farm, nuture, milk and eat them. MERS is if at all a trivial coronavirus corrhyza in such camels, like the common cold coronaviruses cause in humans. This contrasts with the scarcity of MERS cases reported from N Africa- where camel farmers presumably do not cover up as religious law makes the Saudi citizens do.

And it correlates with the epidemic of Ebolain central West Africa- Guinea, Sierra Leone and Liberia , where the chief vector of Ebola seems to be ebola-resistant fruit bats, who live in the dark and have very low vitamin D levels- presumably like their very dark-skinned human compatriots, who presumably also still live largely in the forests or in cities and thus have equally low vitamin D levels; and thus far reported about 25000 suspected cases and 10000 deaths ie 40%; with no antiviral cure in sight; with ?4 deaths in ?18 cases so far reported outside Africa.

These are more reasons to pour safe lowcost effective antivirals vits C and D3 (with balancing vits A, Zinc etc) into such patients and their compatriots at risk. (vit K2 supplement matters only long term against arterial calcification, osteoporosis and cancer in longevity.)

7 March 2015. EPIDEMIC BY power-crazy RELIGIOUS & ECONOMIC EDICT?: MERS: globally ~1040 cases of MERS have been reported. But apparently none outside Saudi Arabia in recent months: So March opens in KSA with 7 day MERS caseload 19 new cases (mean age ~56yrs), and 8 deaths ie total now 939 and deaths 403. . Thats ~20 cases reported the past 7 days there, with 10 deaths ie 50%… in a country in which 18 months and more ago endemicvitamin D deficiency was reported in the Saudi Gazette by their scientists; widely attributed to the obvious cause, that in a land of such abundant sunshine, more so than in any other country in the world, women are obliged by draconian religious law to cover up almost totally outside their houses, and elderly observant men almost as much.

European Journal of Clinical Nutrition , (18 February 2015) Determinants of vitamin D deficiency among undergraduate medical students in Saudi Arabian. BinSaeed, Al-Drees ea A cross-sectional study was performed among 255 first- to fifth-year male undergraduate medical students of a major universities in Saudi Arabia. Results: Majority of Saudi medical students (75.2%) had 25(OH)D levels <30nmol/l = <12ng/ml,. Multivariate analysis showed that the odds of having 25(OH)D serum levels of 30nmol/l were seven times higher both in students who took vitamin D (odds ratio (OR)=7.2, 95% confidence interval (CI)=1.8–29.9, P=0.006) or multivitamin supplements (OR=6.9, 95% CI=1.7–27.3, P=0.006) within 1 year.. There was no significant association between 25(OH)D serum levels and average time spent outdoors per day (P=0.369) and type of clothing (long-sleeved vs short-sleeved; P=0.800). Conclusions: Vitamin D deficiency was highly prevalent in Saudi medical students. Modifiable factors such as vitamin D intake and PA could be targeted for intervention.

Wiki says(and Medscape echoes) that “Immune system: “While it is known that melatonin interacts with the immune system,[53][54] the details of those interactions are unclear. Antiinflammatory effect seems to be the most relevant and most documented in the literature.[55] There have been few trials designed to judge the effectiveness of melatonin in disease treatment. Most existing data are based on small, incomplete clinical trials. Any positive immunological effect is thought to be the result of melatonin acting on high-affinity receptors (MT1 and MT2) expressed in immunocompetent cells. In preclinical studies, melatonin may enhance cytokine production,[56] and by doing this counteract acquired immunodeficiences. Some studies also suggest that melatonin might be useful fighting infectious disease[57] including viral and bacterial infections, and potentially in the treatment of cancer.”

on Pubmed melatonin as an immunomodulator goes back to 1980.

As Wiebke Arlt and Hewison wrote in 2004, “Aging is associated with a decline in immunity described as immunosenescence; paralleled by a decline in the production of several hormones, as typically illustrated by the menopausal loss of ovarian oestrogen production. However, other hormonal changes that occur with aging and that potentially impact on immune function include the release of the pineal gland hormone melatonin and pituitary growth hormone, adrenal production of dehydroepiandrosterone and tissue-specific availability of active vitamin D. It remains to be established whether hormonal changes with aging actually contribute to immunosenescence and this area is at the interface of fact and fiction, clearly inviting systematic research efforts. “

But Observant- aging- Muslims are forbidden the prime cicardian rhythm of outdoor sunshine stimulation of their skin, and in women even their retinae with total veiling. Thus although women are the tougher gender, observant Islam condemns them to be increasingly more compromised goods and chattels than even camels…

There is still no word that the KSA has recently bothered to promote vigorous dosevitamins D3 and C, ( with vit A, zinc, selenium and iodine), as simple safe potential antidotes to their heavily enforced overdressing blockading sunshine-vitamin D3 , that their own medical scientists have repeatedly warned about..

A new report says “Ebola virus is among the most deadly pathogens, with case fatality rates of up to 90%.1 Ebola virus is categorized as a tier 1 pathogen by the US government because of its potential for deliberate misuse with significant potential for mass casualties. The current outbreak of Ebola virus in West Africa with more than 23 000 cases and 9000 deaths2also demonstrates the long-underestimated public health threat that Ebola virus poses as a natural human pathogen. There are no licensed vaccines or postexposure treatments for combating Ebola virus.

But as with pollution, insecticides, road carnage, influenza, TB, HIV-AIDS, malaria, cholera, smoking, sugar, aspartame, alcoholism, it doesnt suit the Big Pharma & Disease Corporates, their paid marketing professors/researchers at universities, and government and hospital/ health industry, to promote avoidance, prevention, cure, natural cheap available remedies like vitamins, minerals and other natural remedies, when disease requiring hospital admission, a patented synthetic vaccine or other drug is far more profitable. . Only Disease Pays.

28 Feb 2015 after a quiet KSA 2014/15 year-end with declining MERS case reports- 11 in December, 20 in January, the past week has seen 18 new cases but 9 deaths in KSA, the KSA totals SINCE 2012 UP to 920 CASES AND 395 DEATHS (43%) ie for February 75cases and 31 deaths. . As always, until the KSA MOH Command clarifies, how many of these are current, versus catchup reports from previous weeks/months, remains to be seen. But as the winter recedes there, the death rate this month remains 41%%….

And in UAEone new (expat) case died this month; and a new case in a nurse returning to the Philippinesfrom KSA is the first case in that country, .. combining KSA with Wiki stats, bringing apparent world totals to perhaps about 1029 cases and 420 deaths.. The deathrate from MERS has widened starkly from 42% in to 30% outside KSA.

8 Dec 2014: HEALTH ADVISORY FOR VISITORS TO OR FROM MIDDLE & FAR EAST, EUROPE, AFRICA, the AMERICAS: The MERS infection outbreak slacks off: – down from the recent 2 cases a day to 25 cases in November with 12 deaths; 4 cases so far this month with 3 deaths- ie the deathrate is picking up. . No more exports reported from KSA since one returned home to Qatar last month. the quadrupled case rate since October has fallen back from 39 cases & 15 deaths a month ; – and deathrate (9 deaths) in October in KSA that doubled to 0.6/day is back to the 55% rate, still awesome for such a rich and sophisticated country.

though MERS is well below that of the ebola epidemic – some 5000 ie almost 40% deaths among 15000 cases so far- that is ravishing central west Africans impoverished by genocidal warlords; not to mention flu, cholera, HIV, TB, polio-and dengue-like illnesses . Two ebola- infectedpeople from W Africa have died in USA, but 8 have recovered in USA from Ebola .

Latest evidence is that the current ebola epidemic is due to bats- human overpopulation causing massive deforestation,displacing ecologically vital bats (never mind vital bees, birds and butterflies) from their natural habitat. Liberian workers who flew to USA and Germany with Ebola died; but 8 of 9 infected cases have recovered there; as have infected European health workers. .. . .

But West Africans are reportedly trying to flee to South Africa to escape the epidemic. and 9 out of 16 Medicine sans Frontiers staff who contracted ebola died. .Is ebola falling there? or are patients simply hiding, dying outside hospitals?

14 Oct 2014The first MERS case outside KSA was reported yesterdayin Qatar, in a returnee from KSA, ie thats 5 cases this week contracted in KSA, reportedly bringing world total to 892 cases and 356 deaths.Croft says Over the past 30days Saudi Arabia has reported 17 MERS infections, 9 of which were from the Taif region; which concurs with the KSA stats excluding the backlog of old cases reported last month…Four Saudi males this week with MERS in Jubail, Taif and now Riyadh , and deaths each in Riyadh and Taif.. so Saudi MERS cases there now 10 Cases Under Treatment, 429 Cases Recovered, 763 Total; and 324 deaths ie 43% death rate . In 14 days this month that’s 9 new cases in KSA, 5 deaths, 3 cases recovered; compared to September’s net ?12 new cases. The stats for September (incl 19 deaths) are blurred by the adjustments announced on 19 Sept (with previously unreported cases up to 3 June, with net 16 new cases after other corrections); so the new cases and deaths reported in August may be correct-4 new pts, 4 deaths; and July 9 new cases, 6 deaths; and June 28 new cases? .. .

So the MERS case rate in KSA so far this month has mushroomed from the 0.3/day in July, the nadir of 0.13/d in August, ? 0.4 in Sept, to 0.64/d this month; and the deathrate from 0.2/d in July to the nadir of 0.13/d in Aug to >0.6/d this month.

BUT 6/9 OF THE NEW CASES THIS MONTH HAVE BEEN IN THE GARDEN RESORT CITY OF TAIF 100 KM SOUTH OF MAKKAH- mostly in Saudi men with camel contact. perhaps this may be because of a resevoire of MERS in camels there. The climate may be favourable for humans BUT ALSO FOR MERS- October temps of 15 to 30c, humidity of 40%, 11 mm rainfall.’

MORE ON OPTIMAL VITAMIN D3 DOSE, AND THE DIFFICULTY OF ACHIEVING CLINICAL OVERDOSE: Four new reports highlight how difficult, and important it is to achieve adequate optimal bloodlevels of vitamin D with vigorous vitamin D3 supplements, let alone overdose with any significant adversity: note three used the recommended vitamin D3, not the long-condemned mislabeled Lennons/Aspen vitamin D2 (which is misleadingly labelled “caciferol” without disclosing that it is D2 not D3). Even a single 2 million iu overdose of vit D3 in nonagenarians had no adverse effect-since the bloodlevel was back to zero by 3 weeks, thats above 100 000iu/day on average…....continue..

8 Oct 20141st Ebola case diagnosed in Dallas USAin a Liberian visitor, who died today (one of > 4000 deaths in W Africa estimated so far); and a new case in Spain, the first infection outside Africa. Ebola anxiety spreads.. It is alarming that the MERS deathrate is not falling but rising there-5 new MERS cases already this month, vs 12 in Sept, 5 cases in August; and now 8 deaths in past 38 days..

VITAMIN D3 DOSE:We get excellent results in outpatient adults with loading oral dose of vit D3 of about 200 000 to 400 000iu depending on illness severity and body mass; then pro rata about 50 000iu per week till better, tapering to fortnightly when well; pro rata in kids...continue..

​​​​​​30 Sept 2014 another new Mers case in KSA, a 70yr old Saudi man in AlMadinah.

“The last report issued December 2013 for the previous 3 months by the USA Department of Justice (Vaccine Court), for compensation made by the USA Services for people injured or killed by vaccines – available as a Power Point presentation – 139 claims settled , with 70 of them being compensated. So, just over 50% of the claims filed for vaccine damages were compensated during this period. Once again, the greatest percentage of damages compensated were for the influenza vaccine, and most of those were for Guillain-Barré Syndrome (GBS). Yet these facts, in a Department of Health website, are never reported in the mainstream media. Read the report yourself in the Power Point file here. Of the 70 cases compensated, 42 ie 60% were for the flu vaccine. The combined total of the other 40% of cases settled included the following vaccines: Hep B, Tetanus, HPV, DTaP, MMR, IPV, PCV, Hib, Meningococcal, Varicella, TD.

29 Sept 2014 MAJOR SAUDI UPDATE: FRESH MERS FLAREUP WORSENS: There have lately been 3 new cases, (2 Saudis and an expat), near Mecca; 2 in Riyadh- and now death of a 38yr old previously well Saudi woman in Riyadh.

Thats 3 MERS deaths; and 4 new cases – Saudis- in central KSA the past 10days, 11 this month; contradicting the puzzlingly optimisticcomment this week from KSA health ministry’s Fakeih that “MERS is not an issue in Saudi anymore. We are doing all we can to have a safe Hajj for all our guests.” If MERS is not an issue, why is the new caserate there picking up, and the deathrate not falling?

the KSA Ministry‘s recent audit found some 19 previously unlisted MERS cases in the 10 week April -May 2014 surge – all but three of the cases were in Jeddah- plus some false positives , and changes of status..

The totals there now are 8 Cases Under Treatment, 426 Cases Recovered,753 Total; and 319 deaths ie 42% death rate .

But outside KSA there have been no further MERS cases or deaths reported for months, so thats apparently worldwide 885 cases , deaths 353 = 40%. But the deathrate outside KSA remains only 26%. and outside Arabia the deathrate remains 10/30 ie 33%. Despite the surge in KSA in the ~10 weeks mid-March till early June, before the peak summer season in the Northern Hemisphere, the ongoing outbreak in KSA (14 cases there since the month’s lull till mid-August) contrasts with the last MERS cases reported outside KSA in early-mid-July about 10 weeks ago –2 cases in Abu Dhabi ie the UAE, & 5 in Iran. .

So thats a total in KSA of 20 more new cases and 13 more deaths than was reported before the audit on 12 Sept. Of the KSA 749 total, 27% were healthcare workers; 65% were Saudis- the vast majority this season in Jeddah and Riyadh; ​​​​61% male; 4% under 16yrs, 45% between 16-45, 27% 45-60. and 24% 60+ years. ie approx 15% of all cases in every 15year age bracket from 16yrs up, but only 4% in the first 15 years. Deathrate was “only” ~18% in EACH OF the three 15year agebrackets up to 45 years, but 45% in the 46-60yr olds; and quadrupled to 80% over age 60years.Thus unlike eg flu, only in the KSA elderly is MERS par excellence a highly risky infection .

MERS IN KIDS: the likely number in KSA extrapolated from 4% of 749 cases is about 30 kids under 16yrs; but the new KSA bargraphs show ~18% deaths in kids ie about 5-6 died. so the child deathrate has doubled from 9% 1/11. In Dr Memish’s April paper there were only 11 pediatric cases positive by screening and confirmatory PCR for MERS-CoV reported from Saudi Arabia. Two patients were symptomatic and the other 9 cases were asymptomatic.The median age of patients was 13 (range 2-16) years. There were eight females and three males (2.7:1 ratio). One symptomatic patient died (1/11 = 9%) and the other symptomatic patient recovered. The diagnosis of patients was based on positive nasopharyngeal swabs on the majority of the patients. Most cases of childhood MERS-CoV infection was asymptomatic and tested positive during contact investigation of older patients. Severe disease can occur in children with underlying conditions.

So in KSA with a mean population age close to 20 years, the age distribution of MERS is roughly spread across adult lifespan, sparing (with both low incidence and low mortality) children who make up almost half the population. This is the opposite of the claimed swine flu severity in kids in the “pandemic” of 2009. Perhaps in KSA this is as expected since generally schoolchildren take more dairy products, get more exercise, sunlight, fresh produce and supplements, and wear less sun-exclusive clothing- supporting vit D+C deficiency evidence as the proximate cause of MERS-CoV susceptibility in KSA adults..

So despite repeated published warning from the top KSA scientists that their conservative (ie covered) dress and diet code puts Saudis at very high risk of known vitamins C & D & Zinc deficiency, the blackout on acknowledging this and promoting vigorous vits C and D3 & Zinc supplements continues, with 80% death risk for the elderly and 20% for every child who contracts MERS in KSA. Until proved otherwise by simple trial of vigorous supplements, this denial, omission in fact may be culpable homicide on the part of KSA authorities- especially as the KSA, with a mean annual income per head similar to UK and western Europe and with similar Caucasian origin population, notoriously has life expectancy 5 years lower than that of UK and much of the North Atlantic lands. .

12 Sept 2014 Bad news strikes KSA with the Hajj in full swing- after 3 clear days, 2 new MERS cases but not in the eastern provinces like the last cluster, this time one each in Riyadh and the Mekkah region, both Saudis, both in ICU; but not the usual seniors- a 38yr old male with previous health issues; and 28yr old female, neither of them healthcare workers. So now the KSA numbers are 28 under care; 399 recovered; 729 total; 302 died.

Yet Drosten, Memish ea from the international Corona Virus Study Group write in the NEJM this week: “Transmission of MERS-coronavirus in household contactsis only 5% in 26 MERS index patients and their 280 household contacts. Strategies to contain the MERS-CoV depend on knowledge of the rate of human-to-human transmission, including subclinical infections. The median time from the onset of symptoms in index patients to the latest blood sampling in contacts was 17.5 days (range, 5 to 216; mean 34.4d“.

This again confirms the obvious, that the virus, like the common cold, is low virulence and transmissibility EXCEPT in the frail and elderly – who (perhaps like many overworked hospital workers) in KSA who as reported there apparently get little sunshine, little vitamin D3, and likely little vitamin C. The rate of MERS in students, kids, farm workers, labourers remains very low, presumably because they get plenty of sunshine. And no article/report on MERS from KSA – where all adults are forced to cover up their skin outdoors- says that anyone is encouraged to vigorously top up their vits C and D3 levels.
​​​

OUTCOMES: triangulating cases scantily reported on the KSA MERS website with 30 new cases since mid-June, 5F (28-55yrs, 4 Saudis) and 25 men; there have been 8 deaths all in men between 38 and 80yrs old. The high deathrate in the men may be because their average age was about 59yr vs 41yr in the women.

August: 5 new cases (1 Saudi female; 1 male an expat HCW; 2 of the men- 69 and 72yrs, Saudis, chronics, died within 3 and 6 days respectively ),

July:10 cases; 2 Saudi female; of the 8 men, 2 are HCW , 2 expats- one of whom died the same day aet 73yrs.

24 August 2014: 12 days free of new MERS cases in KSA. but on 22 Aug the death of another male, a 66yr old expat, was reported in Riyadh, this totals 23 Cases Under Treatment, 399 Cases Recovered; 301 cases passed away, (May Allah have mercy upon them). * Total 723 Cases. 44.8% dead or impaired.

​​​​But Alghamdi ea from the KSA Govt & Universities, and Lincoln University UK have this week published The pattern of Middle East respiratory syndrome coronavirus in Saudi Arabia: from June 2013-May 2014 ie some 425 cases (before the recent June “discovery” of another 100+ cases there). This study deduces that the outbreak thrived especially in Riyadh and Jeddah with high temperature and low humidity ie summer desert conditions; older men being at much higher risk than their kinswomen. . But once again, the paper studiously avoids the obvious reasons why KSA is at the hub of the MERS storm. The authors like the KSA authorities totally ignore the repeatedly published studies by their own academics the past decade, and even by USA authorities like Prof Mike Holick, that Saudis have markedly low vitamin C and D and even zinc levels. And their increasingly orthodox overdress as they age and have more leisure time drastically increases their vitamin D deficiency.

This comes back to usual Media and Governmental Semmelweis denialism , persisting with the myth that good diet and prescription medicines are enough. In fact balanced nutrition with fresh natural produce is becoming a rarity even in stable progressive urban cities, and the resultant epidemics of infections let alone degenerative diseases are in most cases due, (apart from deliberate pollution especially with plastics, estrogenics , pesticides, endocrine disruptors eg phthalates, heavy metals including fluorides, bromates; dioxin etc, radioactivity, and high refined carbs, and inadequate fish oil and medium chain triglycerides and water intake), to micronutrient deficiencies especially of vitamins C, D3, K2, and crucial minerals like magnesium, zinc, iodine, selenium, chromium etc.

Modern infectious outbreaks like the resurgence of influenza, polio, TB, HIV and MERS, and hemorrhagic fevers like Ebola and Marburg, are arguably as others have proposed deficency diseases – eg scurvy, since all the severe infections listed, never mind acute bacterial infections, have been shown for almost a century to respond dramatically to highdose vit C, vit D3 and some zinc, and multivite (A,B), without antibiotics or much benefit from eg ARVs or tuberculostatics. .

So thats 326 patients in KSA who died or are still impaired by MERS, who might have been spared by simple highdose vits (D3 + C) supplement-at trivial cost, no major adverse effects, but massive evidence of protection and cure against all serious diseases; in a population at long-known high vits C+D3 deficiency risks. .

The question remains: why are (inter)national authorities ignoring all the published evidence linked below, that vigorous dose vitamin D3 supplement eg 5000iu/kg loading dose then 1500iu/kg/fortnight eg 100 000iu every two weeks , plus a few grams of buffered vitamin C a day, drastically reduces all diseases including virus infections?

12 August 2012 KSA reports (after a month free of new cases) despite peak summer there, two new previously chronically ill Saudi cases in two days: a 72year Riyadh man; a 59 year old man far south of Riyadh; and death of a previously reported apparently formerly well 74 year Riyadh Saudi man. But they dont say when these recent elderly Saudis took ill or died. Total in KSA now 723 cases, 41% deaths. 28 cases under treatment ie 45.2% dead or impaired. ..

To put MERS in perspective, Ebola in Central Africa this year has infected over 2000 cases, 50% deaths, probably worsening the >100 000 malaria deathrate per year in the region, globally >200 million cases a year with a million ie 0.5% deaths.. .. Mosquito-spread Chikungunya virus spreads from Africa/Asia to over 570 000 people across the central Americas .. … .

9 Aug 2014 still not over: NOT THE END OF THE ARABIAN MERS CoV OUT- BREAK- STILL MORE QUESTIONS THAN ANSWERS, : its now 30 days since the last reported MERS case – BUT the fact is that the KSA Bulletin chillingly reports “As of 12 pm 9 Aug, 2014: 1.” still 27 Cases Under Treatment 2. 396 Cases Recovered. 3. 298 cases passed away (May Allah have mercy upon them). total 721 case.so 30 days after the last recorded new case, 27 patients there are still suffering from MERS sequelae – for at least four weeks duration now, likely now permanent?. .

27 cases out of 721 total reported in KSA is only about 4%. But since these 27 cases remain under care a month after the last reported new case, they must now be at best approaching chronically impaired, if not on renal or respiratory assistance. ie the total of dead and impaired rises to 325/721 = about 45%. More important, KSA has apparently not yet released an analysis of the demography and primary and secondary causes of death of these cases- presumably by MERS definition, respiratory and renal . This analysis is urgently needed. All we know for certain is that there was a MERS outbreak apparently in one of their Dialysis units; and that the outbreak was especially bad in health workers especially hospital staff.

COMBINED SEVERE ACUTE RENAL AND RESPIRATORY FAILURE: Forty years ago we (Burman ND, Austin M, Thatcher GN ea) delivered a review of Groote Schuur Hospital experience at a local South African renal congress on the high mortality of combined acute renal and respiratory failure in the age of hemodialysis and ventilators, respiratory intensive care, antibiotics and immunosuppression. . Apart from the common major sepsis, trauma and allergic eg antibiotic causes, the obvious “primary” cause – which any virus eg MERS-CoV may mimic- , is the “autoimmune” hypersensitivity Goodpastures Syndrome GPS – which untreated has a mortality of ~80% but with modern treatment perhaps 20%. This is half the deathrate reported in KSA from MERS. There is no shortage of respiratory and renal ICU and dialysis, advanced medical specialists in KSA centres. So from GPS perspective, much better salvage might be expected.

“GPS is rareaffecting about 1ppm (0.5-1.8 per million people) per year in Europe and Asia.[5]The peak age ranges for the onset of the disease are 20-30 and 60-70 years.[5] It is also unusual among autoimmune diseases in that it is more common in males , less common in blacks than whites. This may partly explain why the inhabitants of the dromedary-exporting Horn of Africa have been spared MERS outbreaks.

A recent reviewfrom Germany gives the mean time from onset of MERS to acute renal failure of only 11 +-2 days (c0mpared to 20 days in SARS). It is well reported that those contracting acute MERS are already sufferers from major chronic illnesses eg diabetic- cardiorenal-respiratory ie heavily predisposed to immune failure if not already in renal failure.

Humans have some four primary excretory/detox systems: hepato-gastrointestinal; skin; renal; and lung. In Arabia, water is scarce, the desert climate is hot and dry, and the obligatory dress for the observant almost total body cover by robes. So MERS SARRS is high risk especially as it knocks out the two main excretory systems- renal, respiratory, and in very high ambient temperatures also the skin; except for the affluent minority who have aircooled spacious private homes and offices; with often a reported element of viral gastroenteritis, akin to influenza. .

The mystery remains: why is the UAE reporting 73 cases/9.2million ie 8 per million, but only 12% mortality, compared to the adjoining KSA 721 cases/30 million ie 24 per million? with 93% of world MERS cases recorded from KSA and UAE, and all cases anywhere traceable back to the Arabian Peninsula. The KSA and UAE urgently need to publish an analysis of the demography and pathophysiology of their MERS cases. Is it mostly indigenous Arabs who are contracting and especially dying from MERS in these countries, or also many foreign workers, mainly malnourished labourers?

In the UAE ie Emirates, Wiki says in 2013 UAE’s total population was 9.2 million; 1.4 million Emirati citizens and 7.8 million expatriate ie 16.6%Emirati(citizenry), 23% other Arabs, 54.4% Asians, and 6.0% other expatriates. Thus the relatively democratic & liberal UAE has only 40% Arab ie (majority also Wahhabi) Muslim population, compared to some 90% in the KSA. . in 2005, 76% of the total UAE population was Muslim, 9% Christian, and 15% other (mainly Hindu). Census figures do not take into account the many “temporary” visitors and workers while also counting Baha’is and Druze as Muslim.[65] Among Emirati citizens, 85% are Sunni Muslim, while Shi’a Muslims are 15%.

The comparable life expectancyin the bigger but relatively poor mostly caucasian countries of Europe is 80 yrs (Portugal), 81 (UK) to 83yrs , and 84.6 in Japan. Why the richer KSA has so much lower life expectancy can only be due to combination of culture (overdress?) and perhaps genetics- but Israel, also a predominantly eastern mediterranean semitic people, like Europe has life expectancy of 82.1 years. on that tabulation, UAE expectancy is 79.2yrs, USA 79.8, but KSA only 74.3.

Comparison of Grossdomestic product and per capita income for 2014 fail to explain the differences in life expectancy ie survival between the highest earning countries, with KSA, UAE, Israel and much of the middle east countries falling in the $30 to $40 000 per capita income bracket.

NO NEW CASES WORLDWIDE: 4 suspected MERS cases investigated in Hong Kong after arriving there via Dubai have proved negative for MERS.

8 August 2014 Ebola virus disease EVD update – West Africa Disease outbreak news Between 5 and 6 August 2014, a total of 68 new cases of Ebola virus disease (laboratory-confirmed, probable, and suspect cases) as well as 29 deaths were reported from Guinea, Liberia, Nigeria, and Sierra Leone. On Wednesday, 6 August and Thursday, 7 August, an Emergency Committee determined that the current outbreak constitutes a Public Health Emergency of International Concern. and advised that: it constitutes an ‘extraordinary event’ and a public health risk to other States; the possible consequences of further international spread are particularly serious in view of the virulence of the virus, the intensive community and health facility transmission patterns, and the weak health systems in the currently affected and most at-risk countries.

It was the unanimous view of the Committee that the conditions for a Public Health Emergency of International Concern (PHEIC) have been met. New cases and deaths attributable to EVD continue to be reported by the Ministries of Health in Guinea, Liberia, Nigeria, and Sierra Leone. Between 5 and 6 August 2014, 68 new cases (laboratory-confirmed, probable, and suspect cases) of EVD and 29 deaths were reported from the four countries as follows: Guinea, 0 new cases and 4 deaths; Liberia, 38 new cases and 12 deaths; Nigeria, 4 new cases and 1 death; and Sierra Leone, 26 new cases and 12 deaths.

As of 6 August 2014, the cumulative number of cases attributed to EVD in the four countries stands at 1 779, including 961 deaths. The distribution and classification of the cases are as follows: Guinea, 495 cases (355 confirmed, 133 probable, and 7 suspected), including 367 deaths; Liberia, 554 cases (148 confirmed, 274 probable, and 132 suspected), including 294 deaths; Nigeria, 13 cases (0 confirmed, 7 probable, and 6 suspected), including 2 deaths; and Sierra Leone, 717 cases (631 confirmed, 38 probable, and 48 suspected), including 298 deaths.– mortality rate so far 55%.

29 July 2014the first Wiki update in weeks indeed shows no reported increase in KSA cases with 41% fatalities; but total Arabian Peninsula cases up to 825 with 321deaths ie 39% fatalities, and 96.3% of global – 855 cases and 331 deaths ie 39%.

28 July 2014 THE END OF THE ARABIAN MERS CoV OUTBREAK? its now apparently 18 days without new MERS cases reported from KSA , compared to 6 cases in the previous week… . so the Wiki figure of WHO-reported cases in the Arabian Peninsula (plus the 2 recent cases in UAE) totals 814/(835 globally ie 97.5% of reported world cases), with 315 Peninsula deaths ie 38.7% fatality rate- but only 13% in the far less coverup- restrictive UAE with its huge foreign worker population. . . supporting the studies of KSA scientists of more severe vit D deficiency in the most covered-up observant people, citizens of Saudi Arabia and its fellow ultra-observant Wahhabi bordering neighbour states (except the UAE) to the south and east. .

and Central Africans are very darkskinned, and the masses malnourished from rampant genocidal wars, so they will have the lowest levels of vitamins C and D3.

20 July 2014 MAYBE.. JUST LACK OF REPORTING? NO COMPLACENCY YET: Giuseppe Michieli‘sA Time’s Memory to 17 July shows 17 more reported MERS cases (all outside the KSA -still 721 cases, 297 deaths): globally 852 with 329 deaths; Arabia 829 with 319 deaths; ie rest of world 23 cases and 10 deaths- similar mortality 41% in Arabia compared to 43% in the 23 infected cases who returned to their own countries (middle east, north Africa, Europe, USA, Malaysia, Philippines) not on the Arabian peninsula- from their visit/working there or, rarely, contact with returnees. . So has the outbreak stopped in the past 10 day

ps the USAEBN radio website reports startlingly different case numbers in far fewer nations, especially tenfold more cases in Qatar and half the number in UAE. Time will tell. . this high occurrence in Qatar is not reported anywhere else? on 24 July it reports for KSA alone 834 Cases (897 in the Arabian Peninsula); 288 Fatalities. globally 873 cases with death rate only 35%. still the massive discrepancies with startlingly far more cases in Qatar and Philippines and far less in the UAE. This website claims, perhaps not implausibly, that “Government Organizations Do not want to publish total numbers of cases for fear of panic, USAEBN will be trying to track it.”

Virologist Dr Ian MacKay IN MID JULY puts the world total of cases at 846 in his informative analysis of age and gender demography.

But with neighbouring Iraq in civil war breakdown and even polio flareup, who knows how many there are suffering and dying from unmonitored MERS CoV.

14 July 2014 The UAE reports 2 new cases of MERS CoV – the first in a long time-, bringing their total to about 73 cases, 9 deaths ie 12% fatality. .KSA reportedone new case 10 July ie 4 past week, and 5 in each of the the previous few weeks; with no deaths, tally now 721 cases, 295 deaths ie 41%. The UK Gov travel warning is about terrorism in the region, not MERS.

The vexed question of the method of spread of MERS CoV between animals- dromedary camels- and humans continues to be hotly debatedbetween expert virologists and camelmen. The KSA has still not issued [ any restriction on camel imports from the suspected source of the MERSCoV- the Horn of Africa.

But the argument is irrelevant for practical purposes. Tradition, belief dies hard, like the strictly enforced hijab overdress, and camelkeeping: “Riyadh’s camel market stretches several miles along a highway out of the city. It’s not true. Camels occupy a special place in Saudi society, We live, sleep, eat and spend our whole lives with camels, we drink their milk, its a medicine.. There’s no disease,” said a trader at the market”. Its the story of 160 years ago, the cholera-spreading London’s Broad St water pumpuntil Dr John Snow recognized and stopped the source of the cholera diarrhoea epidemic. This far more lethal KSA lung-kidney epidemic is simpler- encourage people worldwide to get plenty of free natural sunshine , or if living at far north darker latitude or practicing hijab and unable to sunbathe- especially over Ramadan- take at negligible cost vigorous supplement of vitamin D3 to a high safe bloodlevel .

8 July 2014 Spread of MERS CoV- Down but not out: from 15 cases a day in early May, now KSA has reported 8 new cases past 7 days; ie 720 total, 294 deaths- 4 new cases past 3 days, with 1 new death. 18 new cases in 24 days since 13 June. So the rate of new cases is not dropping there the past month – or simply more cases being tested and reported. Only sick cases who see doctors, and their contacts, and city health workers, are likely being screened.

The death rate in KSA since the outbreak 2 years ago remains 40%. why should this be? other than that Saudis do not benefit from the midsummer as do other populations- they remain shrouded in overdress and thus severely vitamine D deficient? and the virus seems to spread not airborne but by direct contact – human to human, or camel-(milk?)-human? and the KSA has not yet been reported to have stopped mass camel importation from the Horn of Africa for butchers to supply meat.

Theretirees are the elderly, generally frailer, probably more at leisure, more orthodox ie more ritually overdressed? and circulating /concentrated more through/in the cities especially Mekkah, Riyadh, Jeddah, and visiting the more frail and sick worldwide; thus more susceptible.

Healthworkersare obviously the most stressed and hardworking, exposed to concentration of symptomatic MERS cases and thus ingestion and surface (if not droplet) contamination .

This also favours nutritional ( sunlight/vit D/C/zinc) deficiency as a significant factor in susceptibility of retirees and healthworkers to MERS. The general population (unless seriously ill with other disease) is largely immune to MERS, like flu and common colds, in them the MERS CoVirus seemingly causes nothing more.

4 July 2014 frail pilgrims should postpone the Hajj this year. the European Centre reportsKSA 716 cases, 293 deaths; worldwide 843 cases (817 in Arabia incl now 4 in Iran), 322 deaths. in 21 countries, ie 21 cases outside the Middle East (ie outside the camel contagion area south-east across the Arab states that have had 791 cases so far) . So thats about 10 new cases over the mid summer in KSA the past 15 days so far. Only 1 new death. Case reporting from the rest of the world lags behind.

Certainly frail pilgrims – especially with diabetic and cardiorenal/respiratory diseases -all over the world will be wise to postpone. And the KSA is at last considering stopping import of camels (4.7 million a year mostly for human consumption, – mostly from Somalia, which has never reported a MERS case) – from the Horn of Africa- their main meat supply. This appears to be the source of the outbreak- simply camel colds that kill only sickly humans who unlike camels avoid sunshine by edict… . Up to April 2014, it was predominantly a disease of older men; (it appears that camels are men’s work); but by midMay the male dominance in human MERS cases was fading.

But is the core problem the well-camel MERS-Covirus carriers? It is in fact more likely that the prime cause is that the entire KSA population is at extreme risk – both because those who can afford it overdress by religious edict, especially upperclass Muslim women in total coverup and thus badly vitamin D deficient; and because the KSA imports vast numbers of mostly poor unskilled foreigners to do mostly manual work. Such poor labourers are usually undernourished, living in poor conditions, and with poor access to medicines and medical care until they collapse; and unless outdoor labourers, living and working long hours indoors, and hence also badly vitamin-D and C deficient. . TheWiki review Saudi Arabia “Foreign workers estimated them to number 1/3 of KSA residents recently. Saudi Arabia has become increasingly dependent on foreign labour, and although foreign workers remain present in technical positions, most are now employed in the agriculture, cleaning and domestic service industries. The hierarchy of foreign workers is often dependent on their country of origin; workers from Arab and Western countries generally hold the highest positions not held by Saudis, and the lower positions are occupied by persons from Africa, the Indian subcontinent, and Southeast Asia. the situation has persisted because of a reluctance by Saudis to take on menial work and a shortage of Saudi candidates for skilled jobs.[.. The Saudi economy has, therefore, remained dependent on importees for expertise in specialized industries, and on the Asian workforce for the construction industry, menial and unskilled tasks.[8] Saudization is generally considered to have been a failure.[10]

THE MERS-CoV CAMELTRAIN FROM AFRICA: This again begs the huge question: if camels carrying asymptomatic airways MERS CoV are indeed the virus vector from Africa – almost 5000 a year from Somalia alone- imported into KSA through Jeddah port, WHY ARE THE EXPORTING CAMEL- TRADERS and camel- breeders IN NORTH AFRICA NOT SUFFERING vastly from MERS respiratory-renal syndrome? They are likely Muslim if not black Africans; oil-rich Arabia employs vast numbers of overseas expats as labourers, and outside the KSA, Arabia especially the UAE hosts hundreds of thousands of non-Muslim professionals. But unlike say Indians and other Asians, Pinoys and Malaysians are mostly Muslim, so are more likely to observe cover-up dress code, and thus be more vulnerable to MERS. . This again supports the evidence that the current symptomatic serious MERS-CoV SARRS – Severe Acute Respiratory Renal Syndrome – that occurs in and kills almost exclusively vit D deficient frail observant Muslims – is due to conditioned sunlight deficiency. The north African camel breeders and traders, and the camel herders and camel men in Arabia ( like cowboys on the prairies and herders worldwide in hot climates), are unlikely devout well -berobed Bedouin of Arabia. Camelmen like cowboys get plenty of sunshine vit D, if only via bare faces and arms; and thus can with probable impunity, immunity against MERS, drink raw camel milk and travel with vast camel herds.

27 June 2014 update: (compared to 13 June 2014 KSA 702 cases, 292 death, worldwide 826 cases, 326 deaths): there are now reported in KSA 710 or 718 cases ie 8 -16 in 2 weeks, no more deaths; and globally 833 cases & 322 deaths. . Australian virologist Dr Ian Mckaypostulates why vast camel imports (from Africa, via Jeddah port) for eating is likely the source of MERS in Saudi Arabia. He omits the obvious link in the chain, that the deathrate from MERS CoV is far lower outside Saudi Arabia because this sunny country is the strictest in the world for enforcing Wahhabi hijab total overdress code and thus profound acquired vitamin D deficiency even in men, and worse in females who in public – unlike men- must have even their heads and faces veiled by a niqab- and in pilgrims from other lands who as part of their holy pilgrimage undertake to follow permanently the strict hijab dresscode. Their simple option is to take effective permanent vitamin D3 orally eg 50 000 iu weekly.

IT IS COMMON CAUSE THAT ONE DOESNT, CANNOT PREVENT OR TREAT INFECTION BY POOR NUTRITION OR LOWDOSE ANTI- MICROBIALS- such policy is futile if not dangerous for breeding resistance as well as disease extension. The studies below confirm the obvious, (as Klenner, Pauling, Cameron ea showed the past 50 years with highdose vit C injection), that vitamin D3 orally also works as a multiantimicrobial agent if given as early as possible in safe very high dose and bloodlevel eg 600 000iu monthly (in the first month, – in Salahuddin’s Pakistan PTB patients (presumably also Sunni muslim) initially mean wt 45kg, thats vit D3 ~440iu/kg/d) for two doses ie a mean of 300iu/kg/day over 90days; not the current preventative recommendation of 80iu/kg /day to a safe blood level of around 50-60ng/ml. As Holick has said, with adequate water intake even 50 000iu vit D3 a day ie 1.5million iu/month for months causes no toxicity. Given the 40% mortality rate in the frail Saudi MERS patients, and in acute severe influenza and other serious viral infections, it can be expected that such highdose immediate vitamin D3 therapy orally with eg 600 000iu, combined with highdose vitamin C, zinc and some multivite, (never mind appropriate antibiotics in acute bacterial infection) will similarly virtually eliminate mortality.

But no KSA Govt website mentions this- except the Saudi Gazette a year ago which strongly urged vitamin D supplement in the KSA as even daily sun exposure does not bring most Saudi women above the vitamin D deficiency threshold. It says Since Muslim women can only reveal the hands and face, they may need to be out in the sun for longer than 30 minutes. But the review conspicuously fails to mention that in public outdoors in KSA, women must have even the head and face covered. It also propagates surprising dangerous nonsense that “severe deficiency needs monthly vitamin D injection – “Mom, have you taken your vitamin D injection this month?, when all it requires is an oral daily, weekly or fortnightly dose vitamin D3 at trivial cost.” It does stress “One of the main reasons why vitamin D deficiency is so common in the Kingdom is because there are very few food sources of vitamin D. Foods which have fairly good amounts of vitamin D are fish liver oil, sweet potatoes, egg yolks, vegetable oils, butter, and fatty fish such as salmon, sardines, and tuna,” said Dr. Rasha Jameel, a consultant in family medicine at a local hospital. In the United States, all milk and dairy products are fortified with vitamins A and D, but no such measures are in place in the Kingdom“.

This correlates with a new metaanalysis(in the BMJ this month) of observational studies from Europe and USA, that all-mortality hazard ratio over a mean of 10 years increases by 57% as vit D level falls from the highest to the lowest level. The KSA apparently chooses to ignore that, as this column reported recently from WHO data, despite apparently being the wealthiest country per capita of bigger populations in the world, KSA’s population life expectation is about 5 years lower than eg far less sunny Britain’s; ie KSA all-cause mortality rate is avoidably materially higher. Despite KSA medical professors having reported in studies that most of the KSA population is deficient in vits D and C, the KSA Govt website chooses to ignore this on official websites; unlike other even Middle-Eastern governments promoting vit D fortification or meaningful safe supplements costing trivial amounts.

Even a new study last year from KSA universitiesconfirmed that ” Most commonly consumed food products by Saudi population which are supposed to be fortified by vitamin D are either not fortified or contain an amount less than (apparently from their table 2 ~ half of) recommended by guidelines set for US marketplace”. Even a UAE authority recently stressed “Can fortified milk fight Vitamin D deficiency? Shockingly low levels of D3 among UAE population cannot be rectified by milk alone.” As Holick ea, including a Turkish University 2010 trial report, oral vitamin D3 is far more effective , and safer than, either vitamin D2, or vitamin D injection -never mind much cheaper. This current ostrich-head-in-the-sand denialism by the KSA government is like that of the RSA govt under Presidents Mbeki and Zuma 10-15 years ago about preventing and treating HIV-AIDS – considering that the safe and beneficial daily intake of vitamin D3 is now universally recognized as 4000 if not 10 000iu/day (ie about 80iu/kg/day or pro rata up to perhaps fortnightly) , to a mean blood vit D level of about 60 to 80ng/ml. .

As Prof Mike Holick pointed out a few years ago, “Even in Saudi Arabia, Qatar and South Africa, more than 50% of the population is deficient in vitamin D, all because of their avoidance of sun. Based on some of the literature, it seems that we could probably decrease health care costs across the board by 25% if everybody had optimal vitamin D status.” As Al Faraj ea reported in Riyadh in 2003, Prof Zahid Naeemfrom a KSA university wrote in 2010, “Vitamin D deficiency is an ignored epidemic in KSA and globally“; confirmed by a KSA study by Ali ea in 2012: “Even in a sunny country like Saudi Arabia the prevalence of vitamin D deficiency in young female is high“.. One does not need to speculate why the KSA and all governments globally choose to ignore this inconvenient truth, downplay effective vigorous vitamin C and D3 (sunshine) supplements- such widespread vitamin D and C deficiencies, like cigarette smoking and alcohol abuse, suit governments and Big Pharma- the Disease Industry- in reducing populations growths and creating jobs for the highly profitable Disease Industry and it’s shareholders- for whom Only Disease Pays. Cheap safe natural Prevention Does not Pay since it at least halves sickness never mind disease industry jobs, taxes and profiteering in the global $multitrillion Disease and Diet and Vaccine and Invasive Screening Industry scams.

As Salahuddin ea note, the good results in Pakistan in only 3 months with vigorous INITIAL dose vit D3 contrasts with Two recently published large randomised, controlled trials of conservative vitamin D3 over months that achieved far lower blood vitamin D levels found no difference in clinical outcomes or mortality: after 400,000iu of 25-hydroxyvitamin D3 or placebo were given by Martineau ea in London, UK to 146 pulmonary TB patients – where mean (trough or midpoint) vit D level (after 100 000iu vitamin D(3) or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment) – was surprisingly only 40ng/ml at 56days – ie after a mean of 7000iu/d by 56 days, vs 10ng/ml on placebo)- less than half of the bloodlevel achieved on vit D3 in the Pakistan trial ;

and by Wejse et al 2009 in Guinea-Bissau to 365TB patients – who received 300,000 IUs of vit D3 ie only 100,000 IU or placebo at inclusion and again 5 and 8 months after the start of treatment, ie below 1000iu vit D3 per day over the 12 month trial period “. The Guinea-Bisseau pts thus might have achieved a mean blood vit D level boost of only 10ng/ml.. and now Havers ea (Baltimore)show Low 25(OH)D is common in diverse HIV-infected populations and is an independent risk factor for clinical and virologic failure; Low 25(OH)D was associated with high body mass index (BMI), winter/spring season, country-race group, and lower viral load. Baseline low 25(OH)D was associated with increased risk of human immunodeficiency virus (HIV) progression and death (adjusted hazard ratio (aHR) 2.13; 95% confidence interval [CI], 1.09–4.18) and virologic failure (aHR 2.42; 95% CI, 1.33–4.41). and Shepherd ea (Eurocoord) Low Vitamin D predicts short term mortality in HIV-positive personsOdds of death decreased by 46.0%( P = .04) for a 2-fold increase in latest 25(OH)D level.. In patients with current 25(OH)D

19 June 2014 update no new cases reported from anywhere the past few days, may be because the KSA is not reporting regularly. so the great news is that more than 2 years after the onset of the MERS CoV outbreak in Arabia, no ongoing transmission has been reported from any of the 22 countries so far affected.

THE POLIO SPREADING GLOBAL EPIDEMIC This decline of the MERS outbreak with the heat of summer contrasts sadly with the now-declared global epidemic of wild natural poliomyelitis– which was hoped to be extinct by now, with Hindu- run India being declared polio-free; but now spreading out with mass refugees from wherever war and chaos are successfully ignited by profiteers and fanatics to neighbouring countries. Eg an expanding militant Islamic Wahhabi arc – ie ultraorthodox overdress code – predisposing to vitamin D deficiency? from Asia– Pakistan, Afghanistan, to middle east – Syria, Palestine, Iraq, Israel; to East/West Central Africa eg Somalia, Cameroon, Ethiopia, Kenya, Nigeria, Guinea-Bissau, – with 365 cases reported in 2013. Perhaps more important is zero natural virus cases in Niger and Chad but cases caused by the circulating vaccine derived virus. The wartorn DRCongo and Sudan are likely next polio outbreaks, while Angola has banned Islam because of its perceived militancy. …

And in February, never mind an outbreak of polio-like paralysis in northern California, a new case was reported in a South African neighbour- in Botswana – for the first time there in 20 years –; “Polio virus is endemic in five countries besides Nigeria: Afghanistan, Egypt, India, Niger and Pakistan. Scientists confirmed that the virus isolated from the boy in Botswana came from Nigeria by laboratory tests that showed it was genetically similar to the strain that has been infecting children in Nigeria . In the past 18 months, polio viruses genetically linked to northern Nigeria have caused new cases of polio in nine previously polio-free countries. Besides Botswana, they are Benin, Burkina Faso, Cameroon, the Central African Republic, Chad, Ghana, Ivory Coast and Togo.” So polio is likely to break out in RSA not because of Islamic overdress but because of the masses of war refugees absorbed by democratic dispensation from the polio-afflicted African states to the north, and poor water supplies, sanitation and nutrition, in so many areas in the northern provinces, despite mass polio vaccination. . In Cape Town’s poorer areas’ clinics, we see almost as many foreign pan-African refugees as we do local black Africans.

VITAMIN C & D AGAINST POLIO: but as with flu, HIV, TB and likely all infections, the rescue remedy that the Disease Industry firmly ignores is freely available also against polio (and all other infections – as shown so successfully by Dr Fred Klennerafter WW2 with highdose vitamin C); and at least two published studies in modern times ie on Pubmed (FDA- Ivanov 2006 USA) shows the predictable enhancement by vitamin D3 as an adjuvant of immune response to vaccine against poliovirus- presaged by a 1949 paper from Foster ea Univ Pennsylvania . .

15 June 2014 new case reported in the 23nd country – Bangladesh, arrived from USA via Abu Dhabi airport. But now disproven. CRUCIAL EFFECTIVE VITAMIN D3 DOSING: TRIALS USING SUBOPTIMAL VIT D DOSES AND LEVELS ARE MISLEADING: A major new metaanalysis of the benefit of Vitamin D and RespiratoryTractInfectionsVIDARIS in PLOS 2013 by Sweden’s Karolinska Institute Bergman ea showed that in the 11 relevant trials (published between 2007 and 2012 ie done through the first decade of this century) using vit D3, “Overall, vitamin D showed a protective effect against RTI (OR, 0.64; 95% CI, 0.49 to 0.84). And the average vit D level at baseline was only 24ng/ml, but with the mediocre vit D3 doses used then of average 2000iu/d (300 – 4000iu/day) given for between 7wks and 3 yrs, the average bloodlevel achieved on replacement was only 50% higher at 36ng/ml”.This confirms more direct experience with higher doses that blood level increment, and benefit, is proportionate to vit D3 dose, at least up to the proven speculative safe upper dose of at least 10 000iu/day (whereas the proven safe longterm daily dose is> 50 000iu/day). “More important, the protective effect was larger in studies using once-daily dosing compared to eg monthly bolus doses (OR=0.51 vs OR=0.86, p=0.01)”. This concurs with our experience of major benefit against respiratory infection that is based on published studies giving a loading month’s dose of about 80-100 iu/kg/day ie ~3000iu/kg; then that monthly dose split conservatively eg 50 000iu every week or two depending on mass, and severity of ill-health; to a more successful blood-level of 60 to 100ng/ml. Similarly, the 2014 VIDA trial across USA- Effect of Vitamin D3 on Asthma Treatment Failures in Adults With Symptomatic Asthma and Lower Vitamin D Level, Castro ea, showed “Vitamin D3 for 28 weeks did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma“. But this trial had the same severe limitation as the Swedish metanalysis of vit D3 benefit- it also used only 4000iu/d. “While all were vitamin D insufficient ie below 30 ng/ ml before the trial and half were deficient with levels below 20 ng/mL, supplementation brought levels above the 30 ng/mL threshold for 82% in that group – mean levels were 41.8 ng/mL at week 28 in the supplement group, while the mean stayed in the deficient range for those who got placebo. ” So 4000iu/day merely doubled the bloodlevel to only about 40ng/ml – only about half of the putative optimal dose. These recent studies force us to conclude that bad weather, and bad prevalent respiratory viruses, and especially with major acute, or chronic illness as in those with or at risk of serious infections eg major trauma or sepsis, MERS-CoV, Ebola, malaria, cholera, cancer, diabetics, smokers, asthmatics, bronchitics, AIDS-TB., pneumonia and old age sufferers, and especially hospital, laboratory and clinic- health workers- we should for an average 70kg adult give a loading dose of about 4000iu/kg, ie 300 000iu, then 10 000 iu/d, or 50 000iu every 5 days, or more simply 75 000iu (about 1.5ml of 100cws vit D3 powder) weekly; or at a stretch, 300000 if not 400 000iu monthly. . As the common imported vit D3 powder concentrate is 100 oooiu / Gm ie per 2 ml, it is simple to take the slightly sweetish powder up to 2 or more 4 ml teaspoons ie 200 000 -400 000 iu on the tongue. The majority of residents of developed countries now live urbanised with mechanized transport, and – especially in Muslim or cold countries- dont live and work / walk all day stripped in the sun. The poor malnourished peasants live crowded in ghettoes , and the poorest are generally the darker skinned and therefore make the least vitamin D3. So with rare exceptions, everyone needs the vigorous vitamin D 3 doses discussed above. But at the prevalent bulk vit D3 powder price of at most about US$0,o2 per 100 ooo iu, at a mean population age of around 20 to 25 yrs -outside Europe- it would cost a country of eg 50 million people perhaps $o.5 per head per year ie conservatively $25 million a year to prevent > 90% of common illnesses including drugging and violence consequences. Of course no government can tolerate such massive loss of jobs and taxes in a decimated disease industry that now turns over $ trillions annually – up to 18 % of national budgets. So it’s up to individual adults, especially householders, educators and employees , to see that the cheapest cure-all after clean water – vitamin D3 – at $2/citizen per year- is recommended and freely available.

13 June 2014 KSA now has apparently reported 702 cases, 292 deaths ie 14 more cases, 12 more deaths in past 11 days.. worldwide 826 cases, 326 deaths. And a new multinational vitamin D study confirms why vitamin D3not D2 must be given.TIME TO SWOP FROM MISNAMED “STRONG CALCIFEROL” VIT D2 TO THE REAL VIT D3.6 June 2014 on the 10th anniversary of the SARS epidemic , a new 2013 review (by Japanese epidemiologists) Remembering SARS-CoV: A Deadly Puzzle and the Efforts to Solve Itbrings home the lessons, the similarities between the two recent killer coronavirus outbreaks, in both outbreaks affecting only residents of closed communities (Arabia and China respectively), with carriage of the virus by travelers into their closed kin communities elsewhere. . Especially the problems of hospital confinement, and superspreaders. Sun-blocking culture among the Chinese whereever they live in their ethnic communities is also stressed in modern literature. Lu et al 2012 show very high levels of vitamin D deficiency in Shanghai. The obvious lesson of the past decades was not noted then or now- prevention is better than cure, as in AIDS and pneumonia and all other infections, simply by superboosting the immune boosters within sensible limits – sunshine/vitamin D3 and C, zinc, iodine, selenium; and for the likely deficient, appropriate iron .. 4 June 2014. Saudi Arabia reports confirm they have indeed uncovered many more cases, as tabulated by the Wiki report yesterday- 689 cases, 283 deaths. Shane Granger in hisRandom Analytics concurs. The graph by the KSA authorities shows that most of the unreported cases reputedly occurred from March through to the first week of May, and that that outbreak is almost over, down from a peak of over 100 cases a week ie at the end of their winter- when vitamin D levels are at their lowest- to about 25 cases a week. .They do not say when the excess MERS-related deaths occurred. Who knows how many more cases and deaths are underreported from the KSA, when the annual Hajj is imminent, and religious tourism is a vast industry for the KSA. This MERS outbreak is in contrast to the 8200 recorded case SARS (coronavirus) outbreak of 2002/3 in China, S.E.Asia, (Canada and USA) and sparsely across Europe – but only 1/4 of the MERS’ ie 9.6% mortality . Just one case was recorded in the middle east and Africa- in Kuwait. Although the SARS and MERS viruses were traced through mammals to bats, the affected populations were genetically different- Chinese versus Arabic ie Caucasian. But a decade after the SARS outbreak, Chinese in Shanghai also had 85% below the vit D insufficiency threshold (30ng/ml) at the end of winter. An International Osteoporosis Foundation study of 2009 showed very high prevalence of vit D insufficiency throughout Asia including China- but worse in Malays. Thus the susceptibility to and mortality from SARS and MERS in the respective races- like Swine flu susceptibility in the frail in USA and Mexico in 2009 and anywhere since- is likely due like any disease to the combination of both socioeconomic burden, genes and sunshine vitamin deficiency. But whereas socioeconomics; genes; and ethnic taboo on sun exposure as in strict Muslims, are not easily correctable, traditional micronutrient deficiency is- especially vigorous vitamin and mineral supplements, without offending cultural taboos.

3 June 2014 update : In the past 5 days, Google websites reported 2 new cases/d in KSA. BUT Wikipedia this evening reports the latest collation: in KSA, 688 cases with 282 deaths ie 41% mortality; this is far higher than in its close 7 Arab neighbours including Iran, with a total of only 89 cases but only 26% mortality. If these figures are accurate, there have apparently been 125 cases in KSA since 29 May ie 25 new cases/day there; but 96 deaths ie 19 per day. But this gross epidemic has not been reported on Google, so hopefully the Wiki MERS tabulation will be corrected- unless it because the KSA was not announcing cases. . Apart from the 8 Middle East nations counted above, the Wiki figures for the outside 16 countries in the rest of the world – 25 cases, 7 deaths ie 28% mortality, are more consistent with reports to date outside KSA, and moderately lower than the fatality rate reported in KSA . All MERS- confirmed cases were contracted in the Arabian peninsula (or from travelers from there). All adults in the KSA including visitors would by edict be almost totally robed when outdoors, the women also with hijab. On the other hand, observant pilgrims from non Arab countries are more likely both older- having chronic degenerative diseases ie more vulnerable- , but likely get more sunshine skin exposure at home, and taking protective supplements before and after; thus possibly explaining the lower mortality and low prevalence of carriage of MERS outside Arabia. The average Saudi Arabian is aged around 20years, but the young there presumably face the same policy against skin sun exposure, and apparently against protective micronutrient supplements. 31 May 2014 Mers update the past 2 days just one new case in Saudi Arabia, but 2 cases in Algeria back from KSA – the 21st country ; and now a total of 6 cases in Iran with 1 death.

29 May 2014: The 26 May Cape Town suspect’s deep nasopharyngeal swab screens have proved negative for Influenza A eg swine flu, and MERSCoV, and she is recovering. . The NICD says they have perhaps 5 requests for screening in returnees from KSA, all negative for MERS CoV. KSA reports 3 new cases past 48hrs , while of recent screened cases there, 4 more have recovered and gone negative. ie 565 cases , but 6 more deaths ie 186 died – 33%; Worldwide thus at least 680 cases / 215 died. But apart from KSA and Jordan (5/10 died= 55%) the fatality rate in the other 19 countries reported is thus also 22.6%, as low as 13% mortality in UAE if their figures are to be believed. The problem is we dont know how many subjects were screened in each country to get the perspective.. Perhaps UAE simply screened many more ‘well’ people with “flu’. of recent cases reported from countries outside Arabia, virtually all presented clinically with serious URTI. Only 2 MERS-COV cases have been finally confirmed in USA, both travelers back from KSA. Thus it is apparent from all the screening patchily reported the past 2 years that: 1. air/physical contact crossinfection between humans (as between camels and humans) is common; 2. but resultant actual colonization (ie the asymptomatic MERS CoV carrier- akin to say the common staph nasal carrier) is reassuringly low- likely in mildly immunocompetent people with suboptimal vigorous eg vit D3 levels and intake of vits C, zinc etc; and cleared naturally within days; 3. BUT of those colonized with invasive MERS CoV who actually present sick enough-ie with MERS– (generally those with comorbidities) to consult doctors, mortality may be > 50% (as eg in KSA, Jordan, Qatar, UK) – likely because they have poorly controlled diabetes, HIV, heart/lung/kidney disease; or very low vit D3 levels and very low intake of vit C, zinc etc. 4. So far survivors of MERS apparently do not stay carriers of the virus. These observations will be simple to affirm/ refute by storing, or immediately testing, all carriers’ and cases’ blood for 25OH vit D3 (albeit expensive) as well as the other obvious markers . But it is harmless and virtually cost-free to treat all such people anyway with vigorous vits D3, C and zinc against all latent/patent diseases. Parallel experience with seasonal flu/ common colds is that while the URTI may have been protracted till the patients consult, virtually all cases quickly resolve with vigorous supplements (vits C, D3, iodine, multivite, appropriate iron, and appropriate decongestants/ “vix” steaming. And of course it is simple and appropriate to deep-sniff pure vit C + D3 powder- as easy as using a nasal sprayer. . 27 May 2014Jordan reports a fresh (10th) case; KSAnow 562 cases –no new cases, but one more death; national school exams start there irrespective.. so global total now may be 650..now 2 in Iran. – – the 21st country?. Its not to say that >650 people have caught the illness, since apart from 30% who died of MERS , at least 20% were well, found only on viral swabs of contacts, ie by definition did not have the MERSyndrome that has killed 30%.. The global authorities have not revealed how many of the balance of 50% of those who screened positive actually developed any flu-like symptoms, as opposed to those who survived pneumonia & renal failure. Vigilance is necessary everywhere since both seasonal (H1N1) flu is spreading in the southern hemisphere, and MERS from Arabia with the recent peak there, and business, social and umrah travelers pouring through the Middle East hubs- especially to and from the worldwide Muslim diaspora , and trade hubs, . . “If you get sick within 14 days of being in the Arabian Peninsula, call a doctor and tell the doctor where you traveled.” said an NBC report earlier this month. 26 May 2041 Our first ‘ground zero’ MERS suspect returnee from Riyadh today screened in Cape Town?: after a weekend with my own flu attending a 3day medical congress here, and bad family news last night, I was caught flatfooted this morning at a walk-in local family practice clinic full of people with sudden flu/gastro gripes: the first lady in (robust, no chronic illness) with usual sudden overnight flu had after two weeks visiting her family in KSA, jetted back from there just two weeks ago, having sat behind a man coughing and spluttering. Before starting highdose supplements etc, she was deep nasopharyngeal swabbed for flu and MERS exam by our South African National Institute for Communicable Disease. Then we will, if she/her family prove positive, contact the airline to start tracing all passengers and contacts here. She is hardly in the risk category that has rocked the KSA. We dont know yet about her flight fellows..

25 May 2014:HOPEFULLY THE MERS SURGE IN KSA IS OVER? latest cumulative Saudi reports are of ~558 MERS cases in KSA, 179 deaths ie ~7 new cases detected a day (none elsewhere) . Thus in the 3 weeks since 3 May, unverified reports mainly from middle east websites are of about 101 new cases ie about 5 new cases a day, and 42 deaths in KSA ie 2/day– ~40% mortality. The rate of new cases presenting and being detected is down, but with the incubation time-lag (5 to 14 days till illness if any), assuming that all sick citizens are promptly tested, the mortality rate will fall next week from its peak a week ago. Tightening protective measures in the KSA and no doubt in all global air-hubs outside KSA are hopefully working- there has apparently not been another reported cases outside KSA the past week. 96% of all cases detected have been in KSA & UAE, with 90% of deaths from MERS being in detected cases there. The lack of new cases reported elsewhere suggests that the global figures are now about 641 cases and 208 deaths ie about 32% mortality. .

22 May 2014 update: in KSA 544 cases, 176 deaths ie so far 18 cases/million, 32% mortality; UAE 7/million; worldwide 661 cases, 207 deaths ie 32% globally. But excluding KSA and UAE, the occurrence of MERS in the rest of the world – including most of the >billion Muslims- has been 50 cases ie Ian Mackay points out, the trend in new cases in KSA is downwards the past month. The common denominator in KSA appears to be that especially city Muslim women there must be virtually totally covered when outdoors in public view.. But as noted earlier in this column, repeated university studies there by their own specialists have shown that their people are especially vulnerable to vitamins D and C deficiency, so easily correctable , a testable hypothesis at trivial cost? This perhaps easily controllable plague is surely an unintended consequence for one of the most highly learned and religiously devout peoples in the world? Is the epidemic growing solely in the KSA because by strict custom, Saudi Arabian residents (and their pilgrim visitors-who also are likely ultraobservant) have to cover up maximally, Dress to Kill? In the rest of the Arabian peninsula the MERS incidence rate is only a fraction? although the deathrate is similar.

19 May 2014 update: KSA toll now 537 cases / 173 deaths ie 31% mortality. The total there was inflated by 19 patients in the Jeddah dialysis unit contracting MERS some time recently. It remains to be disclosed how many of these cases were diabetic, were on vigorous vits C/D supplements, and died? The global figures are now 620 cases tested positive and 202 deaths.

17 May 2014 including a 3rd case (by direct contagion from a newly arrived traveler) in USA, there are now about 650 MERS cases reported worldwide, 200 deaths ie 32% fatalities; 14 new cases daily globally the past 3 days; KSA 529 cases 168 deaths(ie 11 new cases a day; and 16 deaths the past 3 days). But 96% of all cases worldwide to date presented in the Arabian peninsula’s 80 million Arab population, and apparently all 27 outside cases were exports from KSA or their immediate contacts. .. The Wiki entry Tourism in KSA states plainly : “In December 2013, Saudi Arabia announced its intention to begin issuing tourist visas for the first time in its history. Restrictions and security : Visas are only issued for business, relatives of Saudis, transit to a third country, and Muslim pilgrims; general tourism is not allowed.” So effectively in KSA cities there are in public only heavily-garbed Muslims. Apparently now “non-muslim tourists can visit the KSA in a group organized by an accredited agency”, obviously provided they conform to local religious norms. But “A limited tourist visa programme was cancelled in March 2014.[5] Saudi Arabia does not currently issue a visa for tourist travel. Hence apparently the KSA population especially in the cities is overwhelmingly Muslims conforming to orthodox Wahhabi Sunni outdoor attire- although there are apparently some 1 million christians (ie 1:30 of the population -presumably mostly professional/technician experts- in the big cities) in the KSA. Apparently there are over a million camels inthe KSA, (apparently nearly 25million worldwide) with a lifespan akin to humans. “Camels come from neighboring Middle Eastern countries, in part, but also from countries in eastern Africa, including such already beleaguered places as Sudan and Somalia, Nigeria, Tunisia, Ethiopia. Just now online, not scheduled for formal publishing until this summer, is a brand-new CDC report finding widespread evidence of MERS-CoV in African dromedary camels too.” With the dromedary numbers (at least 1 per 30 Saudi citizens), camels’ huge stamina ie resistance to disease, including apparently the MERS virus they carry, their cherished role including as pets, meat, transport, racingstock, and supply of fresh warm milk in KSA society; and the reported low human vitamin D (and perhaps C) levels in the heavily-garbed city citizens, no wonder camels are an ongoing source of the hitherto unknown MERS coronavirus illness for immunodepleted citizens in KSA? whereas the camels themselves apparently suffer no more than a mild cold. A respiratory virus infection in a temperate climate is usually easily thrown off with symptomatic Rx, supplements and plenty of fluids; but on the other hand, in middle east desert temperatures and in all-over robes, hyperthermia and dehydration from MERS may more obvious cause of pneumonia and (pre)renal failure- especially in a population with high rate of sickle cell, diabetic, overweight, cardiovascular and hypertensive disease. Average temperature are about 29-330C ie mean peaks of 40C; with humidity 17% in Riyadh & Medina, but much higher in Jeddah; intermediate in Mecca..

A new report today from WHO chillingly details a party of at least 9 Umrah pilgrims since April 2014 who from Jeddah visited Mecca and Medina and then back via Jeddah to Amsterdam, Greece and USA with developing MERS – from the Jeddah sub-clade which has been identified in at least 30 cases there.. These linkages do not explain why the MERS outbreak has mushroomed solely in KSA residents – not in Muslim communities outside Arabia into which travelers flying home via Jeddah have imported the virus. The co-factor may be that, having inhaled/ingested the virus from human carriers in the KSA, these foreign travelers, often with co-morbidities, were also more vulnerable to the MERS virus because of their adherence to the same all-over dress orthodoxy, and dietary vitamins D & C and perhaps zinc depletion (with or without sickle cell trait) as has been reported prevalent in the KSA; and detailed with references below. A study is awaited of comparative skin shade, diet and skin sunshine exposure (ie degree of conformance to strict Sharia covering) between Saudi Arabians of longterm Arab descent, and their relatives and similarly conforming co-religionists in the distant diaspora Muslim overseas communities that send Umrah and Hajj pilgrims through Jeddah to Mecca and the other shrines. A current wiki-islam websitestresses the serious health hazards (both skeletal- rickets and osteoporosis – and across all system diseases including immune-infection- protection) of full-cover Islamic ie hijab dress through sunlight vitamin D deficiency, unless vigorous vitamin D supplement is taken. It is no surprise that this is as much of a danger for hijab Muslims in high-sunshine desert latitudes as in bleak low-sunshine cities far north.. This might explain why the latest WHOpopulation statistics (perhaps 2011 ie before the MERS outbreak) show that – despite being perhaps the richest per-capita nation (from oil reserves) in the world,- the KSA has expected survival age 5 years below that of UK, especially from combined (hypertension-diabetes-coronary heart- kidney ) disease rate of 375 in KSA vs eg 80 in UK. But even then, a different WHO website showed flu and pneumonia deathrate (before the MERS outbreak) 37 in hot, dry KSA ie 50% higher vs 23.7 in UK. and in about 2011, KSA had a mean population age of 20 years, with annual (agri-and seafood) imports ie dependence of US$17billion, due to its desert-limited agripotential; with predicted rapidly increasing urbanization . It will cost pennies, and a few weeks’ followup of supplement dispensing to KSA citydwellers, (and incoming pilgrims before they leave their diaspora homes for the KSA), of vigorous dose vitamins D3 + C and a multisupplement including the other vitamins , magnesium, zinc, iodine; and fish oil and virgin coconut oil (ie a blanket antioxidant, antiinfection, antihypertensive insulin-sensitizing umbrella supplement) to confirm if the emerging epidemic of MERS (let alone hypertension-heart-diabetes-kidney disease) in KSA is significantly slowed, as common infective and degenerative diseases are here in Cape Town, by such supplements. This simple prospective clinical monitoring of those receiving or not receiving the swine flu vaccine in 2009 was universally recommended, but Authorities refused to enforce such simple monitoring, so there is no clinical evidence that the swine flu vaccine significantly reduced morbidity from the outbreak, which was globally statistically trivial except in the Mexican source outbreak. Similarly, there is no evidence that the spread of MERS-CoV in KSA is epidemic considering that even in the four most densely populated cities – in the three abutting midwest provinces – containing almost half the national population, – the detected spread of MERS illness is still so low (except in the incubator hospitals). Even though camels are so widespread. it is intuitive that rural/desert citizens may take both more fresh (desert) crops (ie vit C) and more vit D- from both camel milk and more sun exposure from outdoor work with more skin exposure in such labourers. Some pictures of camel attendants apparently in the KSA on the internet show bareheaded men in vests. 16 May 2014 the latest KSA stats reported are 515 cases, 160 deaths ie 30% mortality. Globally 621, deaths 189 14 May 2014 now ~592 cases reported in 20 countries – the latest in the Netherlands, and a 3rd case in USA; with ~31% mortality (KSA 495 cases, 152 deaths ie 31%; with 20% asymptomatic). 12 May 2014: USA reports a 2nd case arrives there. a 5th death with MERS has been reported in Jordan. Saudi Arabia reports 8 new cases since yesterday, and 2 more deaths. But as expected, in the KSA eye of the storm , it appears that only contacts of patients are being screened- at least 20% of patients who screen positive for the virus have remained well. So the morbidity and mortality% are in fact very skewed, they are apparently not screening the local population for carriers. The ~28% death rate refers only to deaths in the cohort that were afflicted with MERS and their contacts.

11 May 2014 A new Reuters report today highlights the widespread intimate contact with camels in KSA. “Does the KSA want to control the uncontrollable“? “So far, the reported cases have all originated in Saudi Arabia or in the southeastern part of the Empty Quarter, in the UAE. There are no reports of those outside Saudi Arabia having transmitted the disease to others.“ the past week has seen another ~116cases ~15 cases a day- reported in the Middle East, and another 34 deaths there ie the total has reached ~578 cases (483 in KSA- Kingdom of Saudi Arabia) and ~163 deaths (142 in KSA). So the death rate has fallen to <28% overall. Lebanon and USA become the 18th/19th countries to report a case of a returning traveler. But virtually all identified cases originated in the KSA neighbourhood. The latest figures show that MERS originated and breeds exclusively in the Middle East- (cases per million ppm the past 2 years) in 16 ppm in KSA(483 cases total), 6ppm in UAE (53 total), 3.5 ppm in Qatar(7 total) and 1ppm or less in Jordan (9 total- the first reported cases, in April 2012)) or elsewhere. Apart from the frequency of camels, and the high prevalence of deficiency of vitamin D and possibly vitamin C reported below, ethnic culture may play a major role: In KSA, Qatar and UAE the great majority of citizens are Wahhabi Sunni muslims. By contrast, Yemen is only 65% Sunni, but Oman is distinctly different Sharia culture. Iraq and Iran are predominantly Shia culture.

3 May 2014 four months later: MERS RESURGENCE: NOT A PANDEMIC BUT A DEFICIENCY SYNDROME? more precautions needed: With the recent flareup of MERS Middle Eastern Respiratory Syndrome in the Gulf States, the number of reported cases since New year has more than doubled to 457 ie to >24 cases a week there, but still only in residents/ travelers from/through the Middle East hub, and their contacts; in 17 countries including Europe, Egypt, Malaysia, Philippines and now a traveler from Riyadh to USA. The death toll has reached 133/457 ie the death rate has fallen steeply from 42% last December to 29% overall, understandably as more cases are detected by screening in the source, the Kingdom of Saudi Arabia KSA. Wiki and Reuters seem to give the most update (if not WHO-confirmed) stats. So the evidence so far is that, while camels are endemic carriers there, most recent sick cases have apparently been been traceable human to human transmission – apparently all among Muslims, and in the malnourished or chronically ill older, and health workers as in the case just reported in USA. So there is no apparent spread by other vectors eg bird and farmyard swine as in the case of influenza. Since the reports available indicate that the MERS virus is dangerous only in those already malnourished or with serious other systemic disease, it is like flu- pretty harmless in the well adequately nourished and housed. While frequent flyers are generally well off and well nourished, the same cannot be said for those in virtual ghetto slavery all over the world, eg migrant labourers working on contract in the Gulf States, who have apparently been among the latest victims . So as with the overblown Swine Flu non-pandemic of 2009, there is no good evidence to label MERS a deadly epidemic, it in fact seems to have low cross-infectivity compared to say influenza which spreads like wildfire- but with no more morbidity (except in Muslims?) than the common cold corona viruses.

WHY IS MERS LIMITED OVERWHELMINGLY TO AND SPREADING ONLY IN THE KSA and UAE? is it a unique genetic trait of Saudis? or is it micromalnutrition unique to this ultra-orthodox Muslim nation with unique almost total skin coverup outdoors? why was there no outbreak of MERS in the millions of pilgrims who did the Hadj to the KSA last year? the KSA is 100% muslim, whereas the UAE only 76%, with far more foreigners working and living there. It is common cause that peoples who keep well covered during daylight hours – as ultraobservant Muslim (and ultra-orthodox Jewish) women and men do, have much lower vitamin D levels. Those on restricted diets are also more prone to malnutrition including vit D deficiency, especially if low in dairy products. Common sense perhaps explains why Saudis – in the heart of Islam (Mecca, Riyadh, Jeddah, Tobuk) have low vitamin D and likely also low vitamin C and zinc levels, and thus more infections. Moderate to severe vitamin D deficiency was reported prevalent last year in Saudis by Al-Daghri, Sabico ea from King Saud University Riyadh- where Hasanato in 2006 reported low vitamins A, C and E and zinc levels in severe sickle cell disease. El-Hazmi ea from the Saudi College of Medicine also in 2011 reported that Saudi Arabia and Bahrain have the highest prevalence of sickle cell genes in the Middle East, at up to 18%. Bahrain has just opened a sickle cell hospital, but Bahrain has the tiniest population (1.3million) of the Gulf States although the highest population density, compared to the 38million of the KSA plus the UAE which have had over 90% of MERS cases. Most if not all the camels in Bahrain are in a zoo; whereas in the KSA camels are a favourite if not sacred possession and listed first as the domestic animal. So the absence of MERS in Bahrain is unsurprising.

The UAE on the other hand also has many camels as entertainment if not also for travel – with 5000 camels entered in a beauty contest there alone.. So, despite long days ie much sunshine exposure in Arabia, low fresh water availability likely reduces hygiene (washing and oral hydration) capacity for the masses let alone camels. And the well-covered dress code, and low availability of private sun-exposed balconies and courtyards (unlike apparently more liberal Muslim countries) mean that the Saudi masses do not have the opportunity to get much-needed sun exposure to even the face, neck and limbs let alone the torso.

Hence Saudis have as obvious major risk factors for MERS -not just the teeming MERS reservoir in their valued camels (also a staple milk supply), but more importantly endemic deficiency of vitamins C, D (and perhaps E, zinc) and water compared to relatively less clothed populations in other hot but also better water-supplied countries that also do not carry much sickle cell disease.

Camel meat is apparently no longer a staple in the KSA where staples now include Bread, hummus, rice, and Tabbouleh– a “salad” generally made of parsley, bulgur, tomatoes, garlic, and lemon; Kapsa: the national dish is chicken and rice with vegetables; and Kebab: a base of roasted lamb or chicken and vegetables in pita bread. There seems little vitamin D in that varied diet, especially not pita bread or rice.

Finally, it is common cause from published studies and our local experience that infections eg HI, TB, influenza, herpes and the common (Corona virus) cold are easily treated and prevented by vigorous safe intake of vits C & D combined with the other multivites, zinc, iodine, iron and selenium. In advanced infection cases of eg HIV and TB (in trials from Central Africa and Canada), combining even modest doses of just 2 or 3 of these supplements with appropriate antivirals and antibiotics reduced dreadful morbidity and mortality by two-thirds. NATURAL PREVENTION/TREATMENT: with the theoretical double peril of influenza and MERS- (ie as with the looming Influenza A gastro-/respiratory season in the southern hemisphere), with no proven vaccines or antivirals reported or likely, those in contact with Middle East travelers- or any infection eg flu outbreak- are again reminded to boost their immunity and global health with safe effective lowcost NUTRITIONAL ANTIINFECTIVE supplements: 1.VITAMIN D3 CHOLECALCIFEROL 2500-4000iu/kg/month (not the weak vit D2 ergocalciferol falsely labelled “Strong” Calciferol tabs) most simply taken as a few scoops ie 50 000 to 250 000iu of vit D3 powder/MONTH at all ages (AND IDEALLY target BLOOD- LEVEL 80-100ng/ml depending on overall illhealth state. IT IS VIT D3 THAT IS STRONG CALCIFEROL, NOT VIT D2, since experts report that vit D3 is apparently four times more potent than D2. 2. MULTIVITES with zinc selenium and iodine (and iron for likely deficient eg kids, young women), but especially 3. buffered VITAMIN C ASCORBATE at least 3gm/d orally ( if not with bad infection symptoms – 10 or >30gms / day if not ivi) at trivial cost as powder; to tolerance; 4. with eg ecchinacea, melatonin, garlic, colloidal silver, sutherlandia and whatever other antiviral available locally. Since flu and colds disrupt both sleep and outdoor activity, nothing makes as much sense as co-supplementing both of the day and night hormones melatonin and vitamin D; as well as the other sunshine vitamin- ascorbic acid (solar-produced in abundance in eg fruit) – to improve both sleep, rest and immunity. For small kids/infants the vitamins and minerals can simply be taken as powder in liquid ie in feeding bottle or a glass. It is increasingly notorious how depleted modern breastfeeding mothers (on the industrial polluted fructose-sucrose- aspartame PUFA-antibiotic-hormone-glyophos- GMO laden food chain now prevalent) and baby formulae (unlike colostrum from pasture-fed eg New Zealand dairies) are in such lifesaving immune and anabolic anticancer boosters.

Ironically, recently Prof Zahid Naeem ea from the KSA Qassim Universitypublicised in their university International Jnl of Health Science Vitamin D Deficiency- An Ignored Epidemicin 2010 and 2012 , with prevalence there of up to 80% in the KSA despite the abundant sunshine, thus urging vitamin D supplementation. . But such simple prevention – of all disease but especially wished-for megaprofit pandemics like flu and HIV- is anathema to the multinational Big Pharma and their lobbyists in the global Disease Industry, which employs millions worldwide and generates trillions in income for government and corporates. Prevention does not pay. Simple prevention suits no-one working in the disease and drug and hospital industry since it makes most health workers especially doctors and administrators and hospital largely redundant. It seems that public health officials choose to go on ignoring the deficiency epidemic even in the KSA- unlike Dubai, there is no website of the KSA Govt promoting vitamin D supplementation. The solution is too cheap – and embarrassingly simple. An anonymous bloggerdetails the numerous reasons for endemic vitamin D deficiency in especially the Gulf States.. at least the Dubai Govt publicises the deficiency, and supplementation. Is it irony, or an indictment of the prevailing world-wide largely male-dominated -subservient female culture, that already back in 2001, there were strong warnings about Niqabs and Burqas as Impediments to Health? already in 2012, dairies in the UAE were fortifying milk with vitamin D; and in 2001 academics published a study showing the many reasons for prevalent vitamin D deficiency in the KSA. and Prof Mike Holick in 2010 published an authoritative review The Vitamin D Deficiency Pandemic: a Forgotten Hormone Important for Healthurging vigorous vitamin D supplementation universally. As detailed elsewhere in this column last year, the prophet of vitamin D and melatonin the late Prof Walter Stumpf must be shaking his head repeatedly along with the late Prof Linus Pauling, about the neglect of authorities to promote and distribute vigorous supplements of vitamin C and D3 to the afflicted Arabian peoples let alone worldwide. But then we need to be reminded of the infamous Vitamin Murders, how Prof Sir Jack Drummond was mysteriously murdered with his family on holiday in France in 1952, when he and Linus Pauling were the leading vitamin discoverers and promoters of the 20th century (as Walter Stumpf was of melatonin and vitamin D). The Big Pharma Disease Industry combined with the might of the FBI and the FD could never shut Pauling up; but by whom and why the Drummonds were murdered remains unsolved, thus fertile conspiracy theory. Reading Drummond’s papers on the internet, one can understand why the burgeoning patent drug industry then as now hated natural lowcost unpatentable remedies, unbeatable natural safe antiinfective agents like vits C and D and iodine – each almost universal panaceas. . .

This universal truth about industry suppressing natural remedies is the Semmelweis Paradox, that had the leading obstetrician of his day murdered in his prime by his jealous rivals.

27 Dec 2013 the outbreak not over: 9 new cases; ie overall deathrate 42%, but past 2 weeks 4.5 cases a week just from the KSA.. : Since April 2012, the European Centre reports 175 laboratory-confirmed cases, including 73 deaths, of acute respiratory disease caused by Middle East respiratory syndrome coronavirus (MERS-CoV), have been reported by national health authorities. 27 December, Saudi Arabiaconfirmed nine cases (five asymptomatic healthcare workers and four patients suffering from chronic disease, two of whom had died). 24 Dec 2013 the score now stands at 166 (163 at 16 Dec) cases and 71 fatalities- 42% – in 18 months since the first identified case in June 2012; ie per week – 2 new cases and 1 fatality . No pandemic. No outbreak. Considering the duration of the awareness of the new virus in humans- apparently from bats/camels/swine, even after 18 months of millions of pilgrims visiting the Middle East, and far more foreign travelers flying through those hubs, and intensive surveillance on those routes east and west, the morbidity and mortality have been negligible with only a handful of perhaps related deaths in frail patients. Whether as with seasonal avian ie H1N1 flu from China to the West and south there will be a flareup of MERS-CoV cases in the pending winter from now on in the Middle East, remains to be seen..

12 November 2013 Considering that the Hajj has just ended with millions of pilgrims returning home, and vast numbers of multinational passengers transit through the Middle East hubs, its reassuring that (depending on which reports are duplicates and delayed) only 3 or 5 tested positive cases and 1 or 2 deaths have been reported the past week: especially since only serious flu-like cases are likely to be tested- but more so in the affluent who can afford to fly. So far no reports of MERS-CoV case are apparent in South Africa, although flu-like illness remains common here. Perhaps more people are heeding warnings to take multivites plus zinc plus vigorous vits C and D. The ECDC and OSAP and NowNews and GlobalAlert report As of 11 November 2013, there have been at least 154 laboratory confirmed cases of MERS CoV worldwide, including 65 deaths ie 42% in TESTED cases. All cases have either occurred in the Middle East or have had direct links to a primary case infected in the Middle East. Saudi Arabia has reported at least 125 symptomatic and asymptomatic cases including 53 deaths Jordan two cases both of whom died United Arab Emirates five cases, including one fatality Qatar five cases, including two deaths and Oman one case who has just died. Thirteen cases have been reported from outside the Middle East: inthe UK (4), France (2), Tunisia (3), Germany(2), Italy (1) and Spain (1).31 Oct 2013 with the Hajj over, the latest score is 149 cases and 63 deaths ie 42%. http://www.who.int/csr/don/2013_10_31/en/index.html ie 5 new cases a week from the region, 30% deaths. http://gmggranger.wordpress.com/2013/10/29/quikstats-mers-cov-in-the-arabian-peninsula-nov-2013/17 Oct 2013 with the Hajj in full swing, the latest tally is apparently 139 cases and 60 deaths. So thats only 1 case reported a week the past 4 weeks, and no deaths in that time. Promising news, although we continue to see bad viral-like respiratory-gastro infections in adults locally with the volatile weather.

20 Sept 2013 with below a month to go to the Hajj, the latest Quickstats are 135 cases confirmed, and 60 deaths ie 44% mortality- all new cases and deaths apparently in KSA and the Gulf States. Thus in the past 7 weeks, 41 new cases have been reported ie 6 a week, all in the Gulf States; with unaltered mortality (44%) apparently restricted to the chronically frail. This as the drastically variable Cape Town weather alternates sunshine joy and freezing wet snow or hail, with high prevalence of both respiratory and gastroenteritis attacks, sometimes with protracted debilitating bronchitis; how much of this is local seasonal colds- coronavirus– or flu, orMERS-CoV, or the explosive Norwalk virus, is speculative and academic. Basically So What since management is symptomatic, and vigilant prevention crucially effective with hygiene, home rest and multivites but especially highdose vits D3 up to 10 000 (100iu/kg) iu/day or weekly equivalent plus buffered vit C up to tolerance >100mg/kg/day, zinc, selenium and for the malnourished, iron; perhaps safe plant immune boosters like sutherlandia, garlic etc; and avoidance of smoking, sugar and the likes- boozing and sweetened soft drinks (fructose, aspartame,sucralose).

11 August 2013 OUT OF AFRICA? no new cases of MERS-CoV have been reported the past week; but while camels (in Oman) are now also suspect hosts/ transmitters in the M E, there is some evidence that the MERS virus has the closest virus match yet found to bat CoV in South Africa. As a precaution, with upgrading of shrines in Mecca, KSA is actively reducing overcrowding by Hajj visitors by 20%, and warning the frail and elderly not to go this year. With the prevalent bad winter respiratory and gastroenteritis infections at least around densely populated and polluted Gauteng and KZ-Natal, and especially the floral mountain kingdom of greater Cape Town- all are encouraged to take vigorous doses of vitamins D3 and Superenhanced vitamin C with a broad multimineral-multivite – extra vits A, E, B & coQ10; the minerals zinc, selenium, iodine, colloidal silver, (and iron in the young commonly at risk of deficiency); probiotics ; rooibos or buchu or green honey and lemon tea, sutherlandia; licorice, St John’s wort, garlic, echinacea, olive leaf etc; including sniffing vitamin C ; and if snotty rhinitis/sinus/bronchitis symptoms, steaming with eucalyptus etc.. And during acute attacks especially of respiratory and gastro attacks, avoid sugar, fat, dairy and wheat intake.

2 August 2013 The Hajj to Mecca this year is in the third week of October. While over 15 million (of the world’s ~1.5billion) Muslims visit Mecca – Umrah- annually, some 3 million pilgrims worldwide make the seasonal Hajj visit trip, with pro rata from South Africa only 2000 (of our ~2.5million) apparently the quota of pilgrims allowed this year by Saudi Arabia . But increasing numbers of frequent flyers of all nationalities and races to and from South Africa – Europe fly via the Gulf States Emirates airline, if not commuting to work and visit family there – including professional sports teams for tournaments… So this week’s flood of warning bulletins on the Gulf State respiratory infection outbreak are cause for urgent caution and prevention, perhaps grim news for those who fly that ME route, and their families and close associates and neighbourhoods. The 49% deathrate reported in the now 94 cases- 3 more reported 1 August from KSA- so far from the MERS-CoV Corona Virus MiddleEast Respiratory Syndrome outbreak is alarming, that has spread the past 10 months from the Kingdom of Saudi Arabia KSA and the Gulf States to Tunisia, Europe – France, Germany, Italy- and UK . It is now being recognized as distinct not just from the common cold coronavirus but also from the Chinese Severe Acute SARS-CoV virus outbreak since 2003, of which over 8000 cases have been recognized , but the latter virus having a fatality rate of only <10%; and the current violent but selflimited Norwalk virus gastroenteritis (explosive vomiting and diarrhoea for 1 -3days; (fatality rate <0.1%) raging in UK, it recently is the commonest cause of foodborne infection in USA .

No clinically effective vaccine or synthetic drug treatment has yet been found for these coronaviruses . The same lack of specific antiviral therapy applies against gastroenteritis viruses and influenza, but the mythical 2009 swine flu ‘pandemic’ was even milder (than some seasonal flu outbreaks) with a proven mortality rate far below 1% considering how rapidly far and widely it spread. The reservoir if any of MERS-CoV may be cave bats, (and, ominously, perhaps swine – c/f the 2009 swine flu ‘pandemic’ that wasnt; shades of the deadly Nipah virus outbreak of 1999 – from bats to pigs to man).. But the fact that MERS-Co is spread human to human, and mainly men , has been attributed perhaps to women in strict sharia society being well veiled and thus shielded from inhaling (and transmitting) the air-born virus, never mind womens’ generally stronger immune systems and hygiene, self-care. So beware all those in close contact with recent air-travelers through the ME states and surrounding subcontinent airports – never mind the S-E-Asia airhubs of Hong Kong and Singapore: it maybe only a matter of weeks before cases occur on the other continents especially in city dwellers, public transport commuters, factory and office workers; and who knows, perhaps where bats and swine cohabit close to cities, as around South Africa.. .. Its cold comfort that the latest report yesterday and today, note that this stage is perhaps like SARS in 2002 and swine flu in 2009, the ‘bottom of the iceberg’, with only severe cases being admitted, tested, reported, in already chronically ill frail patients; especially diabetics and renal failure – to which older Muslims are particularly prone; while the virus spreads silently, mildly if not harmlessly in the well majority, as in two young well women health workers in contact with a chronically ill elderly female case in Riyadh, KSA … ANTI-INFECTIVE PROTECTANTS and advice are available from the Natural Remedies Centre, 15 Grove Bldg, Grove Ave, Claremont, Cape Town ph 002721-6831465 or -6717415: Fortunately all Health Shops are well stocked with the many almost 100% protectants against serious infections including fungi bacteria and viruses – colds (ie corona-) and flu’-virus (let alone against all others) afforded by the basket of locally available (although mostly imported) natural lowcost evidence-based nutritionals – supplements the past decades: safe hefty combinations of a number of immune-boosting vitamins, minerals and foods, herbs. This septuagenarian author has, touch wood, on this combination- increased at occasional times of suspected colds-fever- , despite great stress, and flu ‘pandemics’, and avoiding vaccinations, not had a bad infection lasting a day in the past 5 years despite working in the highest risk poor townships and acute hospital clinics with rampant HIV – multiresistant TB cases .

More Canadian and USA studies confirm that vigorous vitamin D need applies especially to those living in far northern USA-Canada and EurAsia etc; but also to all of us globally who spend little time well exposed to the sun- especially the more driven who both live/work indoors and cover even our limbs and heads outdoors as eg more ‘observant’ adults of many faiths do. As a new Creighton Univ study shows, we are at minimal risk of kidney stones on vigorous supplement vit D3 provided we balance it with enough water and magnesium supplement,

This is why in this age of increasing stress, longevity, epidemics, and pollution of both environment and the food and medicine chains, we have for a couple of years now been advocating and taking vitamin D3 – on a century of voluminous evidence (62500 papers on Pubmed alone) since 1914 from top nutritional scientists like Drs Jack Drummond, Linus Pauling, Walter Stumpf, Chris Nordin, Chris Gallagher, Rob Heaney, John Cannell, Bill Grant, Mike Holick, Cedric Garland, ea – at least vit D3 50 000iu a week (~7000iu/d) ie a million units every 20 weeks; retail costing R30 ie R6pm for us aging frailer types (half that dose ie 50 000iu twice a month @R3/month for the poor/ well or small kids).. at R12/US$, that costs all of $3 to $6 a year.

On about 9000iu vit D3 average supplement/day, my total 25OH vit D bloodlevel runs about 90-100 ng/ml ie 220-250 nmol/l. so only 400- 1000iu vit D /day will boost the vit D bloodlevel and benefits little if not trivially.

But vigorous D3 dose must be buffered by vit K2 about >100mcg/day , magnesium about 400mg/d, and the usual basket of other ~50 vits, minerals and other natural supplements, to protect us from kidney and arterial calcification etc. We have previously highlighted trials eg from Pakistan showing that even 600 000iu vit D3 a month ie ~20 000iu/day safely and greatly improves recovery and healing from severe PTB+- AIDS in eg frail Pakistatin patients; whereas overdose of 90year old patients with a 2million iu vit D3 dose (in Netherlands) produced no toxicity. Hence we load sick patients with (an antibiotic-like ) 200 000 to 400 000iu dose before continuing weekly or fortnightly maintenance- with the sickest fattest getting the highest dose, and infants scaled down accordingly (after a loading dose of eg 25 000iu) to eg 1000-2000iu/d, or 50000iu 1/2 scoop ie 25000iu every 2 weeks- the older extrapolation (as for adults) of ~100iu/kg/day.

For the concerned vegan, vitamin D is vegetarian: supplement of vit D2 is extracted from yeast or mushrooms; vit D3 by UV irradiation of cholesterol from lanolin. Like all life, since vitamin D soltriol is a sun-induced sterol oil product (in this case of cholesterol which in turn is built via vitamin C ascorbic acid from plant glucose-sugar), vitamin D does not contain or be made from animal flesh ie animal protein nitrogen any more than does fish oil.

Vitamin D may keep low-grade cancer from becoming aggressive: http://www.sciencedaily.com/releases/2015/03/150322080155.htmTaking vitamin D supplements could slow or even reverse the progression of less aggressive, or low-grade, prostate tumors without the need for surgery or radiation, scientists say. Taking vigorous vits C & D does this for all cancers, all disease.

A Statistical Error in the Estimation of the Recommended Dietary Allowance for Vitamin D. Letter to Veugelers, P.J. and Ekwaru, J.P., Nutrients. 2015 Mar 10;7(3):1688-90. doi: 10.3390/nu7031688. Nutrients 2014, 6, 4472-4475; doi:10.3390/nu6104472. Heaney , Garland ea. 1Creighton University & University of California, San Diego,GrassrootsHealth, Encinitas, CA . Recently Veugelers and Ekwaru published data indicating that, in its dietary reference intakes for calcium and vitamin D, the Institute of Medicine (IOM) had made a serious calculation underestimation [2]. Using the same data set as had the IOM panel, these investigators showed that the Recommended Dietary Allowance (RDA) for vitamin D had been underestimated by an order of magnitude. Veugelers and Ekwaru, using the IOM’s data, calculated an RDA of 8895 IU per day. They noted that there was some uncertainty in that estimate, inasmuch as this value required an extrapolation from the available data, which did not include individuals receiving daily vitamin D inputs above 2400 IU/day.[…].

The Institute of Medicine (IOM) issues dietary recommendations on the request of the U.S. and Canadian governments. One of these recommendations is the Recommended Dietary Allowance (RDA). The RDA is the nutrient intake considered to be sufficient to meet the requirements of 97.5% of healthy individuals [1]. The RDA for vitamin D is 600 IU per day for individuals 1 to 70 years of age and is assumed to achieve serum 25-hydroxyvitamin D (25(OH)D) levels of 50 nmol/L or more in 97.5% of healthy individuals [1]. Serum 25(OH)D is the established proxy for vitamin D status and levels of 50 nmol/L or more have been shown to benefit bone health and to prevent disease and injury [1].

The IOM based their RDA for vitamin D on an aggregation of 10 supplementation studies that were carried out during winter months and at locations with latitudes above the 50th parallel north to minimize the influence of cutaneous vitamin D synthesis [2,3,4,5,6,7,8,9,10,11]. As several of these 10 studies examined more than one supplementation dose, collectively they provided 32 study averages of serum 25(OH)D levels. These are replicated as the green diamonds in Figure 1. The IOM regressed the 32 study averages against vitamin D intake to yield the dose response relationship of vitamin D intake and serum 25(OH)D (green solid line in Figure 1). The IOM further calculated the lower and upper 95% confidence prediction interval based on the 32 study averages and the standard deviation of these 32 study averages (green dashed lines in Figure 1). On the basis of this, the IOM estimated that 600 IU of vitamin D would achieve an average 25(OH)D level of 63 nmol/L and a lower 95% confidence prediction limit (2.5 percentile) of 56 nmol/L. The latter value was rounded downwards to 50 nmol/L to accommodate uncertainty in the estimation [1]. This data point (600 IU vitamin D, 50 nmol/L) is the basis for the current RDA and for the IOM’s conclusion that an intake of 600 IU of vitamin D per day will achieve serum 25(OH)D levels of 50 nmol/L or more in 97.5% of individuals.

The correct interpretation of the lower prediction limit is that 97.5% of study averages are predicted to have values exceeding this limit. This is essentially different from the IOM’s conclusion that 97.5% of individuals will have values exceeding the lower prediction limit. To illustrate the difference between the former and latter interpretation, we estimated how much vitamin D is needed to achieve that 97.5% of individuals achieve serum 25(OH)D values of 50 nmol/L or more. For this purpose we reviewed each of the 10 studies used by the IOM. Eight studies reported both the average and standard deviation [2,5,6,7,8,9,10,11]. These eight studies had examined a total of 23 supplementation doses [2,5,6,7,8,9,10,11]. For each of these 23 study averages we calculated the 2.5th percentile by subtracting 2 standard deviations from the average (depicted by yellow dots in Figure 2). Next, we regressed these 23 values against vitamin D intake to yield the lower prediction limit (red line in Figure 2). This regression line revealed that 600 IU of vitamin D per day achieves that 97.5% of individuals will have serum 25(OH)D values above 26.8 nmol/L rather than above 50 nmol/L which is currently assumed. It also estimated that 8895 IU of vitamin D per day may be needed to accomplish that 97.5% of individuals achieve serum 25(OH)D values of 50 nmol/L or more. As this dose is far beyond the range of studied doses, caution is warranted when interpreting this estimate. Regardless, the very high estimate illustrates that the dose is well in excess of the current RDA of 600 IU per day and the tolerable upper intake of 4000 IU per day [1].

The public health and clinical implications of the miscalculated RDA for vitamin D are serious. With the current recommendation of 600 IU, bone health objectives and disease and injury prevention targets will not be met. This became apparent in two studies conducted in Canada where, because of the Northern latitude, cutaneous vitamin D synthesis is limited and where diets contribute an estimated 232 IU of vitamin D per day [12]. One study estimated that despite Vitamin D supplementation with 400 IU or more (including dietary intake that is a total intake of 632 IU or more) 10% of participants had values of less than 50 nmol/L [13]. The second study reported serum 25(OH)D levels of less than 50 nmol/L for 15% of participants who reported supplementation with vitamin D [14]. If the RDA had been adequate, these percentages should not have exceeded 2.5%. Herewith these studies show that the current public health target is not being met. We recommend that the RDA for vitamin D be reconsidered to allow for appropriate public health and clinical decision-making.

update 1 March 2015: Screening for Vitamin D Deficiency: Is the Goal Disease Prevention or Full Nutrient Repletion?

Since its founding, the USPSTF has sought to provide a firm evidential base for early detection strategies, evaluating such screening methods as mammography and prostate-specific antigen testing. Although it has also evaluated a few interventions, its predominant focus has been testing for markers that identify persons at risk who are likely to benefit from preventive action. Only recently has the USPSTF ventured into the field—or perhaps the minefield—of nutrition, a territory distant from screening tests and risk assessment, with different and unfamiliar landmarks.

The USPSTF presents its conclusions on testing for vitamin D deficiency (1), reporting that it was unable to find evidence for or against such testing. It noted that one of the likely reasons was the absence of a scientific consensus on both the level of vitamin D status that should be judged “deficient” and what the measurable manifestations of deficiency might be. These are also issues for many other nutrients, such as folate, ascorbate, calcium, and protein. Vitamin D may have seemed to offer a way out of this confusion because serum 25-hydroxyvitamin D [25-(OH)D] concentration is generally recognized as one of the best indices of status for any of a broad array of nutrients. Also, it is now readily measurable and widely utilized.

One of the reasons its promise has not been realized is that most studies of vitamin D efficacy have used a disease-avoidance model, which is the standard approach used by the Institute of Medicine (IOM) for most nutrients (2). Furthermore, disease prevention is the explicit focus of the USPSTF. Nevertheless, the IOM and USPSTF approaches effectively equate health with the absence of disease, an equivalence that nutritionists have long rejected. Instead, nutritionists focus on full nutrient repletion when possible. The inevitable gap between disease prevention and nutrient repletion is still largely unexplored territory. For many nutrients, it can be surprisingly wide, as suggested in this case by studies of the intake required to provide vitamin D in human breast milk in quantities sufficient to meet the needs of infants (3). The IOM’s adult requirement for vitamin D is 600 IU/d (4), which is judged to be sufficient to protect against osteoporotic fracture. In contrast, quantitative and empirical evidence indicates that vitamin D intake from breastfeeding needs to be approximately 6000 IU/d (3, 5). Although high compared with the adult recommendation, such an intake almost exactly reproduces the measured vitamin D status of contemporary Africans leading ancestral lifestyles (6). Such populations provide perhaps our best window on vitamin D levels prevailing during the millennia over which human physiology was adapted to its environment by natural selection.

Whatever the actual requirement or 25-(OH)D cutoff may be, there is another likely reason that the evidence is unclear. The USPSTF drew from systematic reviews and meta-analyses of studies of vitamin D effects, such as the one accompanying the current report (7). In general, the criteria for including studies in such reviews are methodological rather than biological. Of the 6 published biological criteria (8) for including published reports in meta-analyses, the review published in this issue met only 2 (comparable basal status and same chemical form), and several of its component studies met none. Including studies that could never have been informative in the first place (especially when they are large) inevitably biases any review toward the null.

What seems not to have been widely appreciated is that vitamin D exhibits flat response regions at both low and high values of vitamin D status, with a sharp rise in the approximate center of the physiologic range of 25-(OH)D values (8). Studies like the WHI (Women’s Health Initiative), which enrolled women with low vitamin D status values and used a vitamin D dose insufficient to move them into the response range, provide little useful information about vitamin D efficacy. Yet, precisely such studies were included in the review by LeBlanc and colleagues (7). This is not to criticize the WHI, which was designed more than 20 years ago (before vitamin D pharmacology was well-understood), but it is to criticize contemporary reviews and meta-analyses that fail to take advantage of newer information or to use critical biological criteria (8) for selection of studies for analysis of biological effects.

In addition, a disease-avoidance approach becomes problematic for micronutrients in general (and vitamin D in particular) when one understands that micronutrients do not actually cause any of the effects simplistically attributed to them. Although necessary for cell response, such micronutrients by themselves do not initiate or cause the response concerned. For example, vitamin D is a component of the biochemical apparatus that opens the genome to allow access to DNA information needed for a particular cell or tissue response. In terms of cell function, this dependence means that when supplies of the micronutrient are inadequate, cellular response is blunted. This is dysfunction, but not clinically manifest disease. Such dysfunction may indeed lead ultimately to various diseases, but disease prevention remains a dull tool for discerning the defect, and a disease-prevention approach clearly does not measure whether the organism has enough of the nutrient to enable appropriate physiologic responses, such as lactation.

Finally, and aside from the USPSTF’s findings, one must ask whether treating without first testing is sound practice. Certainly, it would be rational to do so if the condition being treated is prevalent and the treatment is safe and inexpensive. That is the case with another micronutrient, iodine, and the iodination of salt. However, the current situation is different because consuming sufficient iodine generally does not require conscious adherence to a particular regimen, whereas taking vitamin D does. Usually, testing improves patient adherence because it provides patient-specific, personally applicable information. General assurances that one probably needs extra vitamin D are not as compelling a motivator as knowing one’s number. Thus, whether the practitioner adheres to the widely divergent guidelines of the IOM (4), the Endocrine Society (9), or the American Geriatrics Society (10), measuring vitamin D status seems to be warranted, not so much to diagnose deficiency but to determine patient status relative to the selected guideline.

update 12 Jan 2015 As the poet Juvenal (died 130AD) wrote: Mens sana in sano corporis– a healthy mind in a healthy body. Its great how the prime antistress homeostatic hormones- a pinch of natural melatonin at night, with ENOUGH daytime anabolic soltriol calciferol vitamin D3, restores good sleep, orchestrate homeostasis of all other hormones especially of the crucial adrenals and gonadals and thus thyroid hormones. ..

Thanks to global human (mostly male) greed enslaving the masses the past 7 millennia ie since at least Sumerian times, we have moved rapidly in our lifetime post WW2 from global homeostatic (food, commodities) plenty to a world of dyshomeostasis- cacostasis stress chaos – in most countries from Afghanistan to Zimbabwe. Just a few years ago South Africa led Africa in productivity and skills, and still has the biggest reserves of riches- minerals- in the world; with boundless natural power (sun, sea) and manpower to drive industry and food production. But in 20 years post apartheid, the ruling ANC under Mbeki and the Zumas has with selfserving treasonous greed brought South Africa to its knees with cacostasis, destruction of continuous water, electricity ; school education, organized and quality food provision ie agriculture, social security, the post office, the national airline, health services, Home Affairs and pensions). Now there are rapidly increasing functionally illiterate or old 16 million on state grants supported by the 6 million capable of meaningfully working and paying taxes if they dont emigrate. And state grants have now been extended to age 23yrs because state school leavers are practically unskilled for anything but being labourers. .

The national powergrid and oil reserves have been degraded so that total indefinite blackouts are now imminent, never mind weekly “outages” crippling work- the economy – and destroying appliances. Never mind increasingly pandemic influenza and HIV, antibiotic resistance puts us in the post-antibiotic era in this age of deadly resistant TB and STDs, with reckless immoral leaders like Zuma and Vavi leading the mob in extramarital sex and provoked violence. .

So as never before, everyone from conception to grave needs realistic regular vitamin D3 supplement at about R3 a month to bolster mental and physical health of children, mothers and the working , never mind the ailing aging, to reduce illhealth costs. . Stress- through raised thyroid, sympathetic and cortisol levels and depressed gastrointestinal, cardiovascular, musculoskeletal and immune control, grossly disrupts homeostasis and shifts victims into catabolic estrogen-dominance , insulin resistance mode- which only the hormone supplements D3 and melatonin, and the essential vitamins and minerals if not risk-laden androgenics can try to balance,

George Chrousos ea. University Athens, Greece since Nat Rev Endocrinol.2009 and now Neuroimmunomodulation. 2015 write: Stress – glucocorticoids – and disorders of the stress system- cacostasis vs homeostasis. All organisms must maintain complex dynamic equilibrium- homeostasis- which is constantly challenged by internal or external adverse forces – stressors. Stress occurs when homeostasis is threatened or perceived; homeostasis is re-established by various physiological and behavioral adaptive responses. Neuroendocrine hormones have major roles in the regulation of both basal homeostasis and responses to threats, and are involved in the pathogenesis of diseases characterized by cacostasis – dyshomeostasis. The stress response is mediated by the stress system, partly located in the central nervous system and partly in peripheral organs. The central, greatly interconnected effectors of this system include the hypothalamic-pituitary-adrenal (HPA) axis and hormones arginine vasopressin, corticotropin-releasing hormone and autonomic norepinephrine centers in the brainstem. Optimal basal activity and responsiveness of the stress system is essential for a sense of well-being, successful performance of tasks, and appropriate social interactions. By contrast, excessive or inadequate basal activity and responsiveness of this system might impair development, growth and body composition, and lead to a host of behavioral and somatic pathological conditions.. Glucocorticoids, the end-products of the HPA axis, play a fundamental role in the maintenance of both resting and stress-related homeostasis and, undoubtedly, influence the physiologic adaptive reaction of the organism against stressors. If the stress response is dysregulated in terms of magnitude and/or duration, homeostasis is turned into cacostasis with adverse effects on many vital physiologic functions, such as growth, development, metabolism, circulation, reproduction, immune response, cognition and behavior. A strong and/or long-lasting stressor may precipitate and/or cause many acute and chronic diseases. Moreover, stressors during pre-natal, post-natal or pubertal life may have a critical impact on our expressed genome.

VITAMIN D ECONOMY & GOAL OF SCREENING: Heaney andArmas, Creighton University QUANTIFYING THE VITAMIN D ECONOMY: Nutrition Reviews Dec 2014; and Screening for Vitamin D Deficiency: Is the Goal Disease Prevention or Full Nutrient Repletion? Ann Intern Med.Nov 2014 write:sunlight and food contribute only modestly to the relevant optimal total serum vit D and 25OHvit D levels: unsupplemented individuals who average blood 25OHvit D of 20 ng/mL are receiving about 2,000 IU/day from nonsupplement sources (i.e food and sun) – whites double the amount compared to dark blacks from skin. . It has been established for 30 years that in fair-skinned individuals, a single exposure to UV-B at one whole-body minimum erythema dose can produce a rise in serum 25D that is equivalent to an oral dose of D3 in the range of 10,000 to 25,000 IU, ie by as little as 10–15 min of whole-body exposure at mid-day in mid-summer in a pale-skinned individual. Pale-skinned northern Europeans show a rise in serum 25D of 9 ng/mL (23 nmol/L) at the end of 4 weeks of exposure. By contrast, in dark-skinned individuals, the rise was half ie 4.5 ng/mL . Meat eaters exhibit higher human 25D status . Input gaps left after estimating solar inputs (on the order of 1,300–1,600 IU/day, as noted above) could well be filled by hitherto unrecognized food sources. For example, Taylor et al.21 report a combined (D3 plus 25D) content of 112 IU vitamin D equivalents for 200 g of beef tenderloin or an egg, associated with 2 ng/mL greater level of serum 25D. The Grassroots Health project collects data on supplement type and has found no difference in the 25D concentration achieved with either 5,000 or 10,000 IU daily doses, irrespective of whether the D3 was delivered via a gel cap in oil or as dry powder in a tablet (unpublished data; S. McDonnell, personal communication). vitamin D could be absorbed from orange juice. On the other hand, fat malabsorption syndromes are known to lead to vitamin D deficiency, and the mechanism is generally considered to be a specific impairment in the absorption of fat-soluble vitamin D. However, poor absorption may reflect not so much mucosal dysfunction, as simple sweeping of any fat-soluble compound out of the gut, dissolved in the unabsorbed fat. Dawson-Hughes et al.,35 using pharmacokinetic methods in individuals with normal absorptive function, reported equal absorbability for D3 under fasting and high-fat meal conditions, with slightly better absorption from a low-fat meal. Mulligan and Licata,36 in an observational study of 17 poor responders to oral D preparations, reported greater absorption from a large meal containing fat than from intake on an empty stomach. However, the limited data, taken as a whole, suggest that the effects of dosage form or vehicle are probably small.

Finally, the issue of D2 versus D3 needs brief mention. Formerly considered controversial, there now seems to be a growing consensus37 that, for equimolar quantities, orally administered D3 raises serum 25D by about twice as much as D2.38–42 This has been shown for bolus doses, short-term continuous administration (12 weeks), and long-term continuous administration (12 months).

Intestinal absorption of D3 is mainly from the jejunum and ileum. Absorbed vitamin D can be found in both the portal venous blood and the lymph that drains the small intestine. The lymphatic pathway may have particular physiological significance for orally acquired vitamin D, since it avoids a first pass of the absorbed vitamin D through the liver. This suggests that the quantitative relationship between vitamin D and 25D will be the same regardless of whether vitamin D enters from the skin or the gut.

Diffusion from the skin into the blood is slow, with a half-time of about 3 days.7 This half-time means that when regular sun exposure is the principal source of D3, serum D3 concentration will be essentially constant.

it is reasonably certain that the concentration of vitamin D in fat tissue is substantially higher than the concentration in serum. – a given volume of fat tissue contains approximately 12 times as much vitamin D as the same volume of serum. However, a several-fold gradient is not surprising as D3 solubility in fat is effectively limitless, while DBP capacity, which is large, is finite.

Assuming a diffusional mechanism and a total body fat mass of 35% of body weight, total body stores in an individual weighing 70 kg would range from 900 to 2,800 µg (37,000 to 113,700 IU). Using the calculations set forth in the prior section and applying them to an individual with a serum 25D level of 20 ng/mL, whose metabolic consumption would be ∼2,000 IU vitamin D/day, the total amount in the reservoir would provide enough of a reserve for 18–57 days at that same rate of utilization. At a serum 25D level of 40 ng/mL, that same reserve would support consumption for only 9–28 days. Neither estimate comes close to compensating for the “vitamin D winter” of most temperate latitudes. The smallness of this reserve explains why even outdoor summer workers who had high daytime skin exposure experienced reductions in 25D averaging approximately 20 ng/mL (50 nmol/L) by late winter. Of note, their 25D values had reached >50 ng/mL (125 nmol/L) by late summer, which is roughly the same as that reported for East Africans living ancestral lifestyles.48 This study indicates both that existing stores at the end of summer were not adequate to maintain the achieved summer level and that the late winter level (∼30 ng/mL) represented a utilization of approximately 3,000 IU/day.

Chemical partition Extracellular 25(OH)D The first step in the chemical conversion of D3 is 25-hydroxylation.Bikle et al.51 showed that skin cells contain all the requisite enzymatic apparatus to produce both 25D and 1,25D. However, it is doubtful that under ordinary circumstances, skin is a major source of the extracellular 25D measured in serum (D. Bikle, personal communication). Other sources remain to be identified.

The efficiency with which D3 is converted to 25D varies widely from individual to individual. Various reasons can be put forth for these inter-individual differences that, though studied in somewhat less detail, have been reported by many investigators. One example is the variable methylation of the CYP2R1 gene and, hence, variable expression of the hepatic 25-hydroxylase.53 While there is currently no final answer, it is clear that differences in intestinal absorption of D3 could not explain the slow rise in participant B, relative to participant A. Moreover, the internal consistency in the shape of the respective curves virtually excludes methodological variability as a cause of the difference.

Extracellular 1,25(OH)2D The second hydroxylation, which produces extracellular 1,25D, occurs predominantly in the proximal convoluted tubular cells of the kidney. While 25-hydroxylation is not highly regulated, the opposite is true for 1,25D, the synthesis of which is upregulated by parathyroid hormone and low serum inorganic phosphorus concentration and downregulated by fibroblast growth factor-23. Note that 1,25D is a principal regulator of intestinal absorption of calcium; during this process, it acts by upregulating expression of the calcium transport apparatus of the enterocyte. This is an endocrine effect as it is mediated through serum endocrine-like activity and exhibits a typical negative feedback control loop. Under usual conditions, 1,25D is necessary for regulation of calcium absorption. However, it is not the only factor involved in this process. It should also be noted that in the absence of other vitamin D metabolites, 1,25D by itself has been reported not to be sufficient to elevate intestinal calcium absorption.55,56

As would be expected for regulator molecules, the serum half-time of 1,25D is short (hours). Its concentration in serum is a reflection mainly of relative calcium need—being high in individuals on low-calcium diets or in those with calcium malabsorption and low in individuals with high calcium intakes. Also, 1,25D has long been recognized to be calcemic when used therapeutically. The mechanism is generally attributed to intestinal calcium absorption, but this cannot be a satisfactory explanation, as increased metabolic input alone (i.e., without considering output) is rarely sufficient to elevate the serum concentration of any metabolite. Moreover, 1,25D and its analogs do not elevate calcium absorption in patients with end-stage renal disease,57 a condition in which the calcemic effect of 1,25D is often readily apparent. While not adequately explored, there remains another possibility, i.e., an effect of 1,25D on bone-lining cells, where a fall in bone fluid pH to just below 7.0 is enough to solubilize bone mineral sufficiently to elevate serum calcium.58 Physical partition

The distinction between the endocrine and the autocrine pathways is one aspect of the physical partition between extracellular and intracellular processing of the vitamin. The prevailing assumption seems to be that most or all of the D3 entering the body is 25-hydroxylated and that the resulting 25D circulates in the blood, where it serves as the substrate for both renal and extrarenal 1 -α-hydroxylation, with the renal 1,25D product circulating in the blood like 25D and with the extrarenal 1,25D never being expressed in the only accessible body compartment, i.e., the blood.

As Hollis and Wagner59 have pointed out, D3 enters cells more readily than does 25D and, as noted above, there are several enzymes other than the hepatic CYP2R1 that are capable of 25-hydroxylation of D3.49,50 Hence, a physical partition of the vitamin D pathways prior to the 25-hydroxylation step has to be given serious consideration. That this is more than just a theoretical possibility is suggested by the fact, noted earlier, that oral 25D elevates serum 25D to a substantially greater extent than does oral D3.28–30 This was shown first by Barger-Lux et al.28 in a 10-week dosing study involving the two molecules. Figure 9 plots the 25D response to the two agents observed in a group of 54 healthy adults and shows a clear divergence of the dose response curves, with a greater than seven-fold difference in slopes. Cashman et al.,30 using a different design, found an approximate five-fold difference in response after 10 weeks of dosing, and Bischoff-Ferrari et al.,29 an approximate four-fold difference after 17 weeks of dosing.

Figure 9 Change in serum 25D plotted as a function of intake for varying oral doses of 25D and D3. Data from Barger-Lux et al.28 That there should be a greater rise in 25D when oral 25D is the source is, in a sense, trivial, as oral 25D is immediately reflected in the serum, while oral vitamin D must first be 25-hydroxylated, a process that, as described above, is necessarily slower, sometimes substantially so. Only a proper pharmacokinetic study that compares area-under-the-curve values for the two agents can fully quantify this difference. Such a study must either be long enough to allow the 25D plateau to be reached while on continuous dosing of D343 or, if using a bolus dose design, must follow the time course for the two agents for probably 4 months so as to allow full 25-hydroxylation of the administered D3 and full consumption of the administered 25D. No such data are currently available, and this aspect of the physical partition must remain speculative. Nevertheless, the issue is an important one, not just for the therapeutics of 25D but also for a full understanding of the vitamin D economy (see below).

The 25D half-time (as measured by Clements et al.60–62 using tracer-labeled 25D) presents certain puzzling features in its own right. A half-time of, say, 20 days (toward the lower end of the range found by Clements et al.) translates to a daily turnover of about 3.47% of the total mass of extracellular 25D. If the size of daily utilization is known, it is possible to calculate the size of the 25D mass from that fractional utilization rate. If all of the vitamin D input to the body is converted to extracellular 25D, then at a serum 25D concentration of 20 ng/mL (requiring, as shown above, a daily input of ∼50 µg), that 50-µg input is numerically equal to the daily turnover. So, total 25D mass would be 50/0.0347, or close to 1,500 µg. This figure is larger by an order of magnitude than that of the measurable total serum content of 25D, and the discrepancy becomes even larger at higher serum 25D concentrations or longer half-times. This seeming discrepancy has not been noted previously, with one potential reason being the computational difficulty of harmonizing biological units (IU), first with mass concentrations (µg/mL), then with SI units (nmol). However, if a substantial fraction of daily input of D3 is 25-hydroxylated intracellularly, after which it is immediately activated to 1,25D, then only the 25D in the extracellular compartment would be labeled by a tracer-based approach to kinetic analysis, and the calculated daily utilization of the circulating 25D would be lower and the corresponding 25D mass estimate would be closer to what is known from blood and soft tissue content. These calculations provide support for the suggestion of Hollis and Wagner59 that “parent compound D” has more functional significance than has usually been thought.

There is one quantitative aspect of the physical partition, whether occurring prior to or after the 25-hydroxylation step, which seems inescapable. Whether one takes as optimal a serum 25D concentration of 20 ng/mL or 40 ng/mL, the molar equivalent D3 inputs required to sustain either level are far higher than the moles of 1,25D required to support the calcium economy. As noted above, a serum 25D of 40 ng/mL requires approximately 4,000 IU/day, or 100 µg/day, and a serum 25D of 20 ng/mL requires approximately 2,000 IU/day, or 50 µg/day. By contrast, the calcium economy requires between 0.5 µg and 2.0 µg of 1,25D/day. (Higher doses, as noted above, produce hypercalcemia.) It follows that >90% of D3 utilization is occurring along the intracellular/autocrine pathway. If that is not the case, then most of the D3 input to the body is degraded metabolically and not used at all. The latter possibility seems quite improbable, particularly in view of the marginal or subadequate vitamin D status that seems nearly universal. Answering this question of the relative potency of oral D3 and 25D will illuminate the partition of D3 between the extracellular and intracellular pathways and will be an important step in unraveling the puzzle of the physical partition.

One instance in which the pre-25D intracellular pathway is operative is the transfer of vitamin D activity into human breast milk.59,63 25D does not transfer across the secretory mucosa of the mammary gland with sufficient efficiency to produce enough vitamin D activity in milk to nourish the infant, while D3 does. However, for this to occur, D3 must be present in the blood that bathes the mammary secretory apparatus. In earlier work, Hollis et al.63 showed that the concentration of vitamin D in human milk was about 28% of the concentration of D3 in maternal blood. In subsequent work (B. Hollis, personal communication), that figure was shown to be closer to 32%, and a recent study by Oberhelman et al.64 showed a transfer fraction that can be calculated to be about 44%. Based on recommendations of both the American Academy of Pediatrics and the Institute of Medicine for infant intake (400 IU vitamin D/day, which requires a milk concentration of about 520 IU/L, i.e., ∼34 nmol/L), these transfer fractions would require a maternal serum vitamin D concentration of about 30–40 ng/mL (78–120 nmol/L). (The corresponding 25D concentration would be >50 ng/mL [125 nmol/L]; see Figure 8.) Hollis and Wagner59 estimate that the total input of D3 needed to maintain a milk concentration sufficient to meet the infant’s needs for vitamin D was approximately 6,000 IU/day. The equivalence value derived above produces a needed input of approximately 6,000 IU/day, which is essentially identical to the empirical estimate of Hollis and Wagner. Dosing schedules and serum D3 concentrations

Dosing frequency for oral vitamin D supplementation regimens will affect serum concentration of D3 in predictable and often very striking ways. This fact has been largely overlooked to date, as the serum concentration of D3 has been generally considered to be of no particular interest in its own right. The rationale for infrequent (or bolus) dosing is that it leads to better adherence and that an excess amount ingested today will be stored in fat for use tomorrow. However, this assumption overlooks the effect of infrequent dosing regimens on D3 blood concentrations.

Serum D3 has a half-time variously estimated to be in the range of 0.5–3.5 days, with most investigators favoring a value of about 1.0 days. In contrast, D3 produced in skin moves into the blood with a half-time of about 3 days. This means that when skin synthesis is the principal source of D3, serum D3 concentration will be essentially constant around the clock, as D3 input to the blood from the skin (though produced mainly at mid-day) is effectively constant. With oral ingestion, intestinal absorptive input of D3 occurs mainly during a 4-h period following ingestion. (In one study, a TMAX of as much as 12 h was reported.65 As this is well beyond the usual mouth-to-cecum transit time, the 12-h figure, if confirmed, would suggest appreciable colonic absorption, or small bowel mucosal retention, or a delay pool in the intestinal lymphatics.) In any case, assuming a 1.0-day half-time, serum D3 concentration will inevitably follow a sawtooth pattern, particularly if oral ingestion is the principal input. Figure 10 displays the patterns for purely cutaneous input and for daily, weekly, and biweekly oral administration. With a once-a-week schedule, as is evident from Figure 10, serum D3 concentrations are close to zero for several days each week and below the reference level for most of the interdose interval. Thus, in the practical order, a nursing woman who takes her total weekly dose of vitamin D once each week would produce milk with little or no D content for roughly 4 of the 7 days in each week. This irregular delivery will be even more pronounced with biweekly or less frequent dosing schedules.

Figure 10 Calculated time courses for serum D3 concentration for varying oral dosing intervals. The reference level is the serum concentration for continuous (as contrasted with intermittent) dosing. Each dosing scheme provides the same cumulative intake, according to one of the following regimens: once daily, or 7 times the daily intake once weekly, or 14 times the daily intake once every 2 weeks. It should be stressed that Figure 10 illustrates the concept and is not a depiction of actually measured serum concentrations of D3. Under input conditions in excess of daily use, unused D3 will accumulate in fat, and its concentration there would be predicted to damp the oscillations of D3 concentration in serum to some extent.

An additional feature of interval dosing is the high D3 concentration peaks achieved in the days following each dose. The impact of such high D3 levels is unclear, although Vieth66 has pointed to the induction of the 24-hydroxylation pathway as a likely consequence, with a corresponding reduction in effective vitamin D activity. Further, as the binding capacity of DBP is approximately 4.7 µmol67 (or ∼78,000 IU/L), with true Stosstherapie, as in several recent studies,68,69 the DBP will be fully saturated by the ingested D3, resulting in displacement of both 1,25D and 25D off DBP and into circulation as free or unbound moieties for several days after dosing (i.e., until fat uptake lowers serum D3 sufficiently). This effect amounts to a transient vitamin D intoxication of uncertain physiological import. Unfortunately, there is essentially no published information about vitamin D concentrations in the immediate post-dosing period following large bolus doses. Whatever else may be said of Stosstherapie, it certainly is not physiological. Factors influencing serum 25D concentration

Aside from the possible importance of D3 concentration as the substrate for autocrine activity of vitamin D, there is general agreement that serum 25D concentration is currently the principal indicator of vitamin D status.70 This is because extrarenal conversion of 25D to 1,25D operates at concentrations below the kM for the tissue 1 -α-hydroxylases; hence, serum 25D concentration limits the amount of 1,25D a tissue can synthesize when its cells are stimulated to produce a vitamin D-dependent response. While there is no consensus as to the optimal serum 25D concentration, there is also no disagreement about the importance of the substrate, regardless of which concentration may be deemed optimal.

Input of D3, a factor that manifestly affects 25D concentration, has been the subject of much of the previous discussion. Attention is now focused on the effect on serum concentration of 25D produced by variations in body size and in D3 output, i.e., utilization and/or degradation of the 25D in serum. Obesity

One widely recognized influence on 25D concentration is obesity, with serum 25D being lower in obese individuals. This was originally attributed to a phenomenon termed “sequestration” (implying trapping of vitamin D in adipose tissue of obese individuals).71 However, Drincic et al.72 have shown that simple volumetric dilution is both a more logical explanation and one that fully explains the weight-based difference. Curiously, body mass index works in various regression models almost as well as body weight (and somewhat better in some datasets). This is surprising as body mass index is not a measure of mass but of fatness. The reason is presently unclear, and this observation suggests the possible existence of further mechanisms operating in obese individuals. Parathyroid hormone-1,25D axis Clements et al.60–62 showed that 25D half-time in serum ranged from 15 to >35 days, with 25D half-time being inversely related to parathyroid hormone concentration. The parathyroid hormone effect, noted both in patients with hyperparathyroidism and in animals subjected to calcium deprivation, was, in turn, mediated by serum 1,25D concentration. Why 25D utilization (or degradation) should rise in the face of calcium need is physiologically unclear, particularly as renal 1,25D synthesis is not as dependent on 25D concentration as the autocrine functions of vitamin D.

Inflammation. The other major influence on serum 25D concentration is inflammation. It has been reported that vitamin D status is reduced in the face of systemic inflammatory processes.73–78 For example, Duncan et al.75 reported an inverse correlation of 25D with serum C-reactive protein, with 25D being 40% lower as serum C-reactive protein rose from <5 mg/L to >80 mg/L. Autier et al.,79 in a metaanalysis of the several reports on this relationship, confirmed the existence of the association but attributed the reduced vitamin D status to underlying illness rather than to the inflammation itself. That conclusion may be partly correct, at least for some chronic illnesses, but it cannot apply to the many documented cases in which vitamin D status drops acutely across an inflammatory episode, as with total knee arthroplasty.73,77 In one case study, Henriksen et al.73 reported a 12% drop in 25D by day 2 after total knee arthroplasty and a nearly 80% drop by post-surgery week 8. Reid et al.77 evaluated a series of 33 patients who underwent total knee arthroplasty and reported an approximate 40% drop in total 25D and a 33% drop in calculated free 25D by day 2 after surgery, which was associated with large increases in C-reactive protein.

Decreases in 25D of this magnitude and rapidity cannot be explained by decreased synthesis and must, therefore, reflect increased utilization, degradation, or loss. Depending on which values may be estimated for the total 25D mass (see above), reductions in 25D concentration of the size reported by Reid et al. translate to a loss of several hundred micrograms from the body, which is substantially greater than ordinary daily utilization of vitamin D. While increased utilization cannot be ruled out, it seems unlikely to be the sole explanation. Another possibility, which was suggested by Waldron et al.,76 is the loss of DBP (with its bound ligand) in the urine. In 30 patients undergoing elective orthopedic surgery, the ratio of DBP to creatinine in urine rose 2.5× by the second day post-surgery; this was associated with a >20-fold increase in C-reactive protein. Renal loss could certainly explain much or all of the change in 25D observed in these studies and could be the result of interference with the kidney’s megalin–cubilin system, possibly produced by the anesthesia or inflammatory cytokines associated with the surgery.

Although not directly related to the major focus of this review, the conclusion reached by several of the authors of the studies just reviewed, i.e., that, while inflammation clearly reduced D status, this reduction was without nutritional significance, is in no way supported by data in any of the papers concerned, nor is it consistent with the importance of serum 25D concentration as the principal limiting factor in the autocrine pathway.

METABOLISM AND UTILIZATION the data assembled here make clear that, even with today’s widespread vitamin D inadequacy, total vitamin D inputs are far higher than previously thought, food sources are greater than previously recognized, and solar input, though theoretically capable of fully meeting any plausible vitamin D requirement, is actually only a minor present-day contributor to total vitamin D input at the population level. That does not mean that the human requirement is more easily met. Rather, it indicates that the requirement is higher than previously recognized, with populations still short of meeting that requirement by the amount needed to move prevailing serum 25D concentrations from current values to putatively healthier levels.

These analyses also make clear that at prevailing inputs (i.e., <4,000 IU/day), D3 is rapidly 25-hydroxylated and little D3 circulates in the blood or is shunted into adipose tissue for storage. Additionally, the recent recognition that oral 25D may raise serum 25D to a significantly greater extent than does oral vitamin D suggests the possibility of a hitherto little recognized or explored intracellular pathway in which the entire metabolic sequence is handled within certain target tissues and is not reflected in blood. A related finding in this respect is the importance of a maternal serum D3 concentration sufficient to support production of human milk capable of meeting infant needs for vitamin D.

Several of these insights have implications for the human requirement. For example, the vitamin D input needed to support an adequate amount of vitamin D in human milk has implications not just for lactation but also for human success as a species under presupplementation conditions. Inadequate vitamin D input in newborns would be expected to lead to skeletal abnormalities (for which the paleo-fossil record provides no evidence), in addition to possible consequences for immune system development.89 A total input of approximately 6,000 IU in modern humans equips them to feed their infants with a nearly full range of the nutrients needed for healthy growth.

CONCLUSION Precise quantification of vitamin D inputs, transfers, conversions, and compartment sizes are essential for a full understanding of how the human body utilizes this essential micronutrient, why it is important, and what the consequences are of an inadequate vitamin D input.

Since its founding, the U.S. Preventive Services Task Force (USPSTF) has provided firm evidential base for early detection strategies, evaluating such screening methods as mammography and prostate-specific antigen testing. Although it has also evaluated a few interventions, its predominant focus has been testing for markers that identify persons at risk who are likely to benefit from preventive action. Only recently has USPSTF entered the (mine)field of nutrition, a territory distant from screening tests and risk assessment, with different and unfamiliar landmarks.

The USPSTF now reports it is unable to find evidence for or against vitamin D deficiency testing (1), the likely reasons being the absence of a scientific consensus on both the level of vitamin D status that should be judged “deficient” and what the measurable manifestations of deficiency might be. These are also issues for many other nutrients, such as folate, ascorbate, calcium, and protein. Vitamin D may have seemed to offer a way out of this confusion because serum 25-hydroxyvitamin D [25-(OH)D] concentration is generally recognized as one of the best indices of status for any of a broad array of nutrients. Also, it is now readily measurable and widely utilized.

One of the reasons its promise has not been realized is that most studies of vitamin D efficacy have used a disease-avoidance model, which is the standard approach used by the Institute of Medicine (IOM) for most nutrients (2). Furthermore, disease prevention is the explicit focus of the USPSTF. Nevertheless, the IOM and USPSTF approaches effectively equate health with the absence of disease, an equivalence that nutritionists have long rejected. Instead, nutritionists focus on full nutrient repletion when possible. The inevitable gap between disease prevention and nutrient repletion is still largely unexplored territory. For many nutrients, it can be surprisingly wide, as suggested in this case by studies of the intake required to provide vitamin D in human breast milk in quantities sufficient to meet the needs of infants (3). The IOM’s adult requirement for vitamin D is 600 IU/d (4), which is judged to be sufficient to protect against osteoporotic fracture. In contrast, quantitative and empirical evidence indicates that vitamin D intake from breastfeeding needs to be approximately 6000 IU/d (3, 5). Although high compared with the adult recommendation, such an intake almost exactly reproduces the measured vitamin D status of contemporary Africans leading ancestral lifestyles (6). Such populations provide perhaps our best window on vitamin D levels prevailing during the millennia over which human physiology was adapted to its environment by natural selection.

Whatever the actual requirement or 25-(OH)D cutoff may be, there is another likely reason that the evidence is unclear. The USPSTF drew from systematic reviews and meta-analyses of studies of vitamin D effects, such as the one accompanying the current report (7). In general, the criteria for including studies in such reviews are methodological rather than biological. Of the 6 published biological criteria (8) for including published reports in meta-analyses, the review published in this issue met only 2 (comparable basal status and same chemical form), and several of its component studies met none. Including studies that could never have been informative in the first place (especially when they are large) inevitably biases any review toward the null.

What seems not to have been widely appreciated is that vitamin D exhibits flat response regions at both low and high values of vitamin D status, with a sharp rise in the approximate center of the physiologic range of 25-(OH)D values (8). Studies like the WHI (Women’s Health Initiative), which enrolled women with low vitamin D status values and used a vitamin D dose insufficient to move them into the response range, provide little useful information about vitamin D efficacy. Yet, precisely such studies were included in the review by LeBlanc and colleagues (7). This is not to criticize the WHI, which was designed more than 20 years ago (before vitamin D pharmacology was well-understood), but it is to criticize contemporary reviews and meta-analyses that fail to take advantage of newer information or to use critical biological criteria (8) for selection of studies for analysis of biological effects.

In addition, a disease-avoidance approach becomes problematic for micronutrients in general (and vitamin D in particular) when one understands that micronutrients do not actually cause any of the effects simplistically attributed to them. Although necessary for cell response, such micronutrients by themselves do not initiate or cause the response concerned. For example, vitamin D is a component of the biochemical apparatus that opens the genome to allow access to DNA information needed for a particular cell or tissue response. In terms of cell function, this dependence means that when supplies of the micronutrient are inadequate, cellular response is blunted. This is dysfunction, but not clinically manifest disease. Such dysfunction may indeed lead ultimately to various diseases, but disease prevention remains a dull tool for discerning the defect, and a disease-prevention approach clearly does not measure whether the organism has enough of the nutrient to enable appropriate physiologic responses, such as lactation.

Finally, and aside from the USPSTF’s findings, one must ask whether treating without first testing is sound practice. Certainly, it would be rational to do so if the condition being treated is prevalent and the treatment is safe and inexpensive. That is the case with another micronutrient, iodine, and the iodination of salt. However, the current situation is different because getting sufficient iodine generally does not require conscious adherence to a particular regimen, whereas taking vitamin D does. Usually, testing improves patient adherence because it provides patient-specific, personally applicable information. General assurances that one probably needs extra vitamin D are not as compelling a motivator as knowing one’s number. Thus, whether the practitioner adheres to the widely divergent guidelines of the IOM (4), the Endocrine Society (9), or the American Geriatrics Society (10), measuring vitamin D status seems to be warranted, not so much to diagnose deficiency but to determine patient status relative to the selected guideline.

THE NEAR-IMPOSSIBILITY OF OVERDOSING WITH VITAMIN D3 – except by persistent repeated injection: A Report in Feb 2014 from Bansai & Arora ea New Delhi show how extreme the overdose of vitamin D3 must be to cause hypercalcemic toxicity: an Asian woman given 6million iu imi over 10 days after knee surgery presented 2 months later with 6 wks of persistent vomiting, fatigue, with moderate hypercalcemic renal failure and 25OHvit D level of 150ng/ml; that normalized in 2 weeks.. So her peak level after the initial 2 weeks on an average ~50 000iu/day may have been around 500-600ng/ml.. Bansai and Aroraquote two series from endemically vit D deficient Kashmir (Pandita ea 2012 in Jammu and 2011Koul ea Srinagar) of a total 25 elderly given chronic overdoses D3 600 000iu monthly , who were found to have similar moderate hypercalcemia and renal failure with peak 25OHvit D of 100 – 300ng/ml: a mean vit D3 dose of between 20 000iu and >1million iu/day?, mean s. creat 2.5; mean 25OHvitD of 100 – 200ng/ml; mean calcium 13.1mg/dl. 20 000iu a day indefinitely in these frail small elderly averages at least 400iu/kg/day, at least 5 times the chronic recommended dose in the literature the past decades- and to boot, routinely given them with a highdose calcium supplement- when it is rather magnesium that should if any be boosted. . Koul ea do note that about 100 000iu vit D a day ongoing is required to cause hypercalcemia, the mean lethal dose being about 8million iu.

By contrast, previous reports below- eg from the Netherlands report of 2million iu single overdose in 90 year olds; and planned 600 000iu orally monthly dose in Pakistani men wasted with TB (Salhuddin ea below) showed no overdose signs. So a single loading dose of 1 to 2 million units is unlikely to give overload. By these precedents (eg 600 000iu p.o monthly- apparently official policy of the Pakistani Endocrine Society) one may in acute infections give up to 600 000iu as a loading dose (a million in an obese ill patient) in acute infection situations, then 50 000- 80 000iu weekly depending on weight, to maintain level around 90ng/ml.

Am J Clin Nutr March 2008 Pharmacokinetics of a single, large dose of cholecalciferol 100 000iu Ilahi, Armas, and HeaneyCreighton University Medical Center, Omaha, Design: followed for 4 mo, 30 subjects were supplemented with a single oral dose of 100 000 IU cholecalciferol. 10 subjects served as a control group to assess seasonal change of calcidiol. The subjects were healthy with limited sun exposure (<10 h/wk) and milk consumption (<0.47 L daily); excluded granulomatous conditions, liver disease, kidney disease, or diabetes or taking anticonvulsants, barbiturates, or steroids. Results: Serum calcidiol rose promptly after cholecalciferol dosing from a mean (±SD) baseline of 27.1 ± 7.7 ng/mL to a concentration maximum of 42.0 ± 9.1 ng/mL. Seven percent of the supplemented cohort failed to achieve 32.1 ng/mL at any time point. The highest achieved concentration in any subject was 64.2 ng/mL. The control group had a nonsignificant change from baseline of −0.72 ± 0.80 ng/mL during 4 mo. Conclusions: Cholecalciferol (100 000 IU) is a safe, effective, and simple way to increase calcidiol concentrations. The dosing interval should be ≤2 mo to ensure continuous serum calcidiol concentrations above baseline.

THE IMPORTANCE OF IMMUNOSYNERGY BETWEEN ADEQUATE ANABOLIC HORMONES- VIT D3, MELATONIN(Berman 1926, Carrillo-Vico2013), AND PROGESTERONE in planned and current pregnancy, and aging? Thangamani, Kim ea Purdue & Indiana Universitiesin J Immunol. 2014 Dec 29: Cutting Edge: Progesterone Directly Upregulates Vitamin D Receptor Gene Expression for Efficient Regulation of T Cells by Calcitriol. The two nuclear hormone receptor ligands progesterone and vit.D play important roles in regulating T cells.., we report that progesterone is a novel inducer of vit.D receptor (VDR) in T cells and makes T cells highly sensitive to calcitriol even when vit. D levels are suboptimal. This novel regulatory pathway allows enhanced induction of regulatory T cells but suppression of Th1 and Th17 cells by the two nuclear hormones. The results have significant ramifications in effective regulation of T cells to prevent adverse immune responses during pregnancy.

A recent review of vitamin D from Mike Holick (Boston Mass.) and a German team again reminds us of two opposing forces limiting natural sunshine vitamin D supply: on the one hand the skin shuts down active vit D production if the sunlight burns, while on the other, there is simply not enough sunlight beyond 35degrees latitude from the equator. Thus Germany and Canada-northern USA for example, at >45degrees north, get far too little sunlight for vit D needs ; eg London is at 51degrees north; Cape Town-Florida-San Diego, Sydney-Buenos Aires, Hawai and the Med. countries are at the 35degree south latitude. Even this close to the equator, many overdress- especially more observant religious women- and thus minimize benefit from summer sunshine.

Sunshine Cures: why did TB sanatoria work (before there were antibiotics)? was it indeed the boost of copious sunshine secosteroid antimicrobial soltriol in the skin destroying the M TB porphyrins? or was it belief, then-cleaner air, high altitude, rest, care and better nutrition?

A recent 2009 Mt Sinai NY report of a case of CTB cutaneous TB stresses how rare this skin complication is despite the increasing spread of TB with AIDS- perhaps partly because of the higher prevalence of HIV in poorer peoples in sunnier warmer ie relatively better sunshine-cholecalciferol-endowed climates.

We easily make our optimal vit D3 ~100iu/ kg per day living playing and working outdoors in warm lands. But since we dress more in cooler climates, with aging and dress-conservative cover-up tribal eg Arabic and Hasidic and Mormon customs; and avoid sunburn, and from early middle age lose 3/4 of our skin vitamin D production by 70years, we aging thus need the bulk of our vit D requirements as supplements ie ~7000iu/day or 50 000iu/week.

A century ago, TB, polio, measles, scarlatina, and syphilis were rampant, and infections rather than wars killed most – ending in the 1919 flu holocaust that devastated the family of Dr Sir Arthur Conan Doyle (whereas the Flu pandemic took just one of my parents’ score of siblings- and polio just left my Mom with a limp..)..

2014 is the centenary of recent recognition of the cod liver oil antirickets steroid factor – calciferol/soltriol -briefly misnamed “vitamin” D – by McCollum, Davis (USA 1913) and Mellanby(UK); so that in 30 years by 1945, rickets had been all but abolished in USA. But the recognition of the antirachitic factor was facilitated by discovery in the preceding decade of vitamins A, B and C. The antiscurvy benefit of fresh uncooked coloured crops (and thus their juice) had indeed been recognized for millennia – eg the Royal Navy limejuice- , but a specific micronutrient vitamin deficiency was first only recognized in 1907. Vitamin C ascorbic acid identification also took another 25years . For 90 years, it has been recognized that a lightly cooked exclusively fatty meat diet can provide enough vitamin C (let alone all micronutrients) for health in eg atheroma- and scurvy-free Eskimos and anyone who cares to eat thus (Stefansson ) .

Sadly, the lifegiving vitamins have been diluted, all but eliminated from retail bottled codliver oil, a ml of which now generally supplies perhaps only 125iu vit D, and vitamin A 1000iu … So even a tablespoon supplies only about 1200iu vit D.. The Weston Price Foundation discusses why modern commercial codliver oil is good with its balance of vits A and D– but the vitamin D level is still far too low for cooler darker countries. However we recommend, (apart from far cheaper vit D3 powder 50 000iu/1ml scoop) – a tsp cod liver oil at least 3 times a week because it is the cheapest natural- and with Scandinavian manufacturing controls, safe- source of vital EPA+DHA available as well as some vitamins A and E.

As real summer begins here between the southern oceans, cold winter in the northern hemisphere, we must constantly remind that vitamin D3 cholecalciferol is NOT an exogenous vitamin ie a biological nutrient essential (Funk’s ‘vitamine’, shortened by Jack Drummond because they are not amines to the more appropriate ‘vitamin’) in the human diet ( like vits A, B, C, E & K) because humans cannot make them. . But since we make vit D with light exposure of our skin, since most humans dont get enough sunlight on our skin, it is certainly a conditioned essential anabolic steroid, which like other anabolic steroids (the balance especially of androgens) is vital at optimal blood levels through life for optimal health, healthspan.

Unlike the real vitamins and essential minerals, Calciferol is (like eg CoQ10, alphalipoic acid, nitric oxide, EPA and DHA) made in limited quantities in humans with adequate organ function and sunshine; but none of them generally in anywhere near optimal quantities for healthspan against all diseases. So given humans’ capacity to live well to a century, we need such supplements from youth to ensure chronic health so as to die of old age in good health. .

How does this relate to the death this month of Dr Nerissa Pather? Multiresistant TB contracted on duty 12 years ago eventually killed her, whether or not such high-risk people are ever advised to take the best prevention- zinc, selenium, multivites but especially highdose vit C and D3.

D3 bio-insufficiency fragility and dysimmunity is further complicated since to correct it requires both plenty of skin sunshine exposure, eaten vitamin C and it’s daughter cholesterol, and optimal kidney and liver function. Even then optimal vitamin D3 bloodlevel and effect may be blocked by foolhardy cholesterol blockade eg statins, and by excess intake and thus bloodlevel of vitamin D2 ergocalciferol – which authorities eg in South Africa and USA still negligently promote/ dispense as the dangerously misnamed “strong calciferol”. It is indeed D3 cholecalciferol, not D2 that is the miracle sunshine strong calciferol steroid; egocalciferol dominance, like insulin and estrogen dominance, is harmful, and can and must be avoided. .

So it is increasingly apparent that, just as intake/manufacture of vitamin C the true sunshine vitamin (those colourful veg/ fruit orchards etc) , and thence cholesterol, should each be at least a few gms a day, the human (clothed indoor-dwelling) adult synthesis + intake of sunshine hormone vitamin D3 soltriol should be nearer to 10 000iu ie 250mg/day, or more practically 50 000iu vit D3 a week (at a trivial supplement cost of eg R6/month or $5 a year) for a bigger adult- especially in longer darker winter (starting with perhaps about 25000iu every fortnight for babies) .. of course balanced in most societies with the other supplements especially water, vitamin K2, zinc, selenium iodine and magnesium (and iron for children and reproductive mothers) .

So, how many more millions must suffer and die from lack of the cheapest, best, safest conditioned essential antimicrobial antioxidant anabolic nutrients available?

An undated (post 2003) Pharmacology Bulletin from Canterbury NZ at least gives conservative realistic vit D3 advice: a loading dose of D3 500 000iu , then 50 000iu/month. This compares with our routine loading dose of about 200 000 to 400 000iu to start, then 50 000iu every week or two (proportionate to body mass and illness). But Lennons here negligently still continues to advertise their Strong Calciferol datasheet (updated 2004) as calciferol- last year they in fact confirmed it is D2 ergocalciferol, not cholecalciferol. Only their websitehttp://www.ndrugs.com/?s=lennon-strong%20calciferol confirms that their strong Calciferol is D2; whereas they also make low strength D3 tabs.

From today’s press “The South African Medical Association (SAMA) extends heartfelt condolences on the passing of 38yr old Dr Nerissa Pather on 18th December 2014 . Whilst on community service at a Kwazulu Natal clinic, Dr Pather contracted well-publicised multi-drug resistant spinal TB in 2002 , that rendered her paralyzed and in constant pain. The loss to a communicable disease acquired in the course of duty is an incalculable tragedy. SAMA reiterates its call to all health departments and facilities to ensure that basic TB prevention methods are available to all healthcare workers in our facilities. Sadly, this is not the case in many of our hospitals and clinics and continues to place health professionals at enormous risk. The potential consequences of infection and even acquiring drug resistant TB are tragically evident in the death of Dr Pather. SAMA bows its head to a colleague who has paid the ultimate price in caring for her fellow human beings.”

The tragedy is that with general authoritarian nihilism about universal vitamin supplements- some calling their promotion quackery- unrecognized deficiency eg vit D3, rickets, and vit C scurvy are on the increase even in the more affluent eg USA and in sunnier climates- especially with increasing geriatrics and the frail surviving with eg HIV, TB, cancer, chronic bowel disease, gross overuse of warfarin (vit K deficiency) and statin (CoQ10 deficiency) etc. .

Vitamin D Deficiency in Critically Ill Patientsis rarely considered or treated .. N Engl J Med 2009 Lee, Eisman & Center studied vitamin D status in ICU patients referred to St. Vincent’s Hospital, Sydney in 2007. Among approximately 1100 ICU patients per year, the mean 25-hydroxyvitamin D in 42 referred patients was ~17ng per milliliter, with a high prevalence of hypovitaminosis D . Moreover, three patients died (from metastatic thymic carcinoma, glioma, and lymphoma), and had undetectable levels of 25-hydroxyvitamin D. The current study of ICU patients reveals high prevalence of hypovitaminosis D that was associated with adverse outcomes, independently of hypocalcemia and hypoalbuminemia. Supplementation with vitamin D (at a mean dose of 820 IU per day) before admission was not protective. Vitamin D deficiency is associated with increased mortality.However, vitamin D has pleiotropic effects in immunity, endothelial and mucosal functions, and glucose and calcium metabolism. The association between hypovitaminosis D and common conditions (e.g., the systemic inflammatory response syndrome, septicemia, and cardiac and metabolic dysfunctions) in critically ill patients may be important. Vitamin D–deficient and vitamin D–insufficient states may worsen existing immune and metabolic dysfunctions in critically ill patients, leading to worse outcomes. A total of 17% of ICU patients in our study had undetectable levels of vitamin D. hypocalcemia was identified as a reason for referral in only 5% of the patients. These findings highlight the need for consideration of vitamin D status and supplementation in patients in the ICU.

Arch Intern Med. 2008;168:1629-37 25-hydroxyvitamin D levels and risk of mortality in the general population. Melamed , Astor ea. Albert Einstein College of Medicine, NY tested the association of low 25(OH)D levels with all-cause, cancer, and cardiovascular disease (CVD) mortality in 13 331 nationally representative adults 20 years or older from the NHANES III linked mortality files.In patients on dialysis, therapy with vitamin D agents is associated with reduced mortality. Observational data suggests that low (25[OH]D) are associated with diabetes mellitus, hypertension, and cancers. However, whether low serum 25(OH)D levels are associated with mortality in the general population is unknown. Participant vitamin D levels were collected from 1988 through 1994, and individuals were passively followed for mortality through 2000. RESULTS: In cross-sectional multivariate analyses, increasing age, female sex, nonwhite race/ethnicity, diabetes, current smoking, and higher body mass index were all independently associated with higher odds of 25(OH)D deficiency (lowest quartile of 25(OH)D level, <17.8 ng/mL , while greater physical activity, vitamin D supplementation, and nonwinter season were inversely associated. During a median 8.7 years of follow-up, there were 1806 deaths, including 777 from CVD. In multivariate models , compared with the highest quartile, being in the lowest quartile (25[OH]D levels <17.8 ng/mL) was associated with a 26% increased rate of all-cause mortality (mortality rate ratio, 1.26; 95% CI, 1.08-1.46) and a population attributable risk of 3.1%. The lowest quartile of 25(OH)D level (<17.8 ng/mL) is independently associated with all-cause mortality in the general population.

Subst Abuse Rehabil. 2014 Dec 10;5:121-7. Effects of different doses of testosterone on gonadotropins, 25-hydroxyvitamin D3, and blood lipids in healthy men.Gårevik, Ekström ea. At the Karolinska Inst Sweden, Twenty-five healthy male volunteers aged 27-43 years were given 500 mg, 250 mg, and 125 mg of testosterone enanthate as single intramuscular doses. All doses investigated suppressed the LH and FSH concentrations in serum. LH remained suppressed 6 weeks after the 500 mg dose. These results indicate that testosterone has a more profound endocrine effect on the hypothalamic-pituitary-gonadal axis than was previously thought. There was no alteration in 25-hydroxyvitamin D3 levels after testosterone administration compared to baseline levels. The 250 and 500 mg doses induced decreased concentrations of ApoA1 and HDL, whereas the lowest dose (125 mg) did not have any effect on the lipid profile.

BoneKey Rep 2014:3:479:p1-8History of the discovery of vitamin D and its active metabolites Prof Hector deLuca graphically tells the story of the discovery of the lifesaving sun steroid cholecalciferol D3 between 1913 and its chemical formula in 1937, and then its’ functional chemistry through the 1970s. Until the preWW1 era, nutrition was blocked by false German dogma (von Liebig ea) that an adequate diet consisted of just 12% protein, 5% mineral, 10–30% fat and the remainder as carbohydrate. Such a diet – eg with polished rice, sugar and milled wheat- was shown to rapidly kill humans and animals ie without the essential micronutrient vitamins. .

Belief that this defined an adequate diet was to resurface in postWW2 Western capitalism in USA and UK through the twentieth century.

Then British, Continental and USA nutritional scientists started tearing that myth apart- and today we have the revelation that we need the ancient diet: just an adequate amount of first-class protein (but not soya); the bulk of needed nutritional calorie energy as natural fat (balanced omega 3: omega 6 and saturated medium chain triglycerides, but not transfats which are synthetic), with the balance of energy carbs and protein supplied by coloured veggies; supplying enough of the essential minerals, vitamins and marine oils.

But since most humans are no longer able to live off unpolluted unfarmed marine life or natural rotation-crop and grazed meat farming, but work indoors during daylight hours or, worse, disruptive night shifts, and city deathrates have risen steadily on the mythical low(but synthetic) fat, high carbs diet invented as dogma by Ancell Keys and his food factory cronies, the natural fat and -coloured-veggs -dominant diet rapidly re-establishes itself, with vigorous vit D3 and multivits to supplement the depleted and polluted fastfood chain.

update 22 Dec 2014: as the solstice rolls by, infections especially viral flourish north and south, from flu to gastro , HIV to ebola; HPV to HZV to childhood exanthems;

so more reason to aim for optimal growth, mental and physical health with the peak anabolic antidepressant energizing anticancer antiinfective steroid – cholecalciferol D3 – intake and levels. About 65 000iu a week (with my multivit-multimineral combo) puts my measured trough 25OHvit D bloodlevel at 92ng/ml with normal blood calcium. Women can live long without much androgen apart from frail bones, but not well without vigorous cholecalciferol D3 intake. Humans who live mostly bare mostly outdoors- us naked apes- most of the year closer to the equator make plenty of D3 from sunshine; but the darker our skins, the sooner vit D production shuts down; so most of us need vigorous D3 supplement costing perhaps US$6 a year retail. .

update 19 Nov 2014 when this column on vit D started 5 years ago, there were 46000 vit D entries on Pubmed- this has mushroomed 40% to 61000 (compared now to 46000 on vit A; to 53000 on vitamin C; 37000 on vitamin E; 17000 on vit K; and 133000 on all the 8 B vitamins ); whereas in 2009 there were 272500 entries on all vitamins– now up only 22% to 335 000. ie the papers on the secosteroid vitamin D have risen at double the rate of the vitamins.. (D3 C27H44O and D2 C28H44O, vs testosterone C19H28O2).

As the end-of-year solstice approaches, its time to review the crucial role of giving vigorous doses of vitamin D3, whether via non-burn sunshine, or via the correct lowpressure tanning bed, or directly as vitamin D3 (not vit D2) supplement as appropriate TOGETHER WITH A MULTINUTRIENT PLUS EXTRA MAGNESIUM AND VIT K2. . Ironically, dermatologists would recommend vit D supplement not suntan for what many consider the wrong reason- that suntanning does more harm than good, which it doesnt. :

3. Swanson, Barrett-Connor, ea USA & Belgium May 2014: In a cohort of older men, Higher 25(OH)D2 is associated with lower 25(OH)D3 and 1,25(OH)2D3, suggesting that vitamin D2 may decrease the availability of D3 and may not increase calcitriol.

5. Biancuzzo, Holick ea Boston Mass. 2013 Serum concentrations of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in response to vitamin D2 and vitamin D3 supplementationin healthy adults 18 to 79 years consuming 1000 IU vitamin D2 or vitamin D3 per day for 11 weeksat end of winter was analyzed. Of the adults, 82% were vitamin D insufficient (serum 25-hydroxyvitamin D [25(OH)D <30 ng/mL]) at the start of the study. Administration of vitamin D2 and vitamin D3 induced similar increases (from baseline ~20ng/ml 25OH vit D) in total 25(OH)D as well as in 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, respectively. Compared with placebo and adjusting for baseline levels, 1000 IU daily of vitamin D2 was associated with a mean increase of 7.4 pg/mL (95% confidence interval, 4.4-10.3) in 1,25(OH)2D2, and decrease of 9.9 pg/mL (-15.8 to -4.0) in 1,25(OH)2D3. No such differences accompanied administration of 1000 IU daily of vitamin D3.

7. Sempos CT1, Picciano MF ea . USA J Clin Endocrinol Metab. 2013 Jul;98(7):3001-9..Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES.A reverse J-shaped association between serum 25-hydroxyvitamin D (25[OH]D) concentration and all-cause mortality was suggested in a 9-year follow-up (1991-2000) analysis of the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). We repeated the analyses with 6 years additional follow-up in 15 099 participants aged ≥ 20 years with 3784 deaths, to evaluate whether the association persists through 15 years of follow-up. The reverse J-shaped association became stronger with longer follow-up and was not affected by excluding deaths within the first 3 years of follow-up. Similar results were found from both statistical approaches for levels <20 through 119 nmol/L. Adjusted RR (95% confidence interval [CI]) estimates for all levels <60 nmol/L were significantly >1 compared with the reference group. The nadir of risk was 81 nmol/L 32pg/mL (95% CI, 73-90 nmol/L 29-36pg/ml). The association appeared in men, women, adults ages 20 to 64 years, and non-Hispanic whites but was weaker in older adults. A reverse J-shaped association between serum 25(OH)D and all-cause mortality appears to be real. It is uncertain whether the association is causal.

11 Armas , Heaney ea.Creighton Univ Nebraska. J Clin Endocrinol Metab. 2004 ;89:5387-91. VitaminD2 is much less effective than vitaminD3 in humans.Vitamins D(2) and D(3) are generally considered equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitaminD(2)) available in the U.S. market. Relative potencies of vitamins D(2) and D(3) were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the serumvitaminD over 28 d.. The two calciferols produced similar rises in serum concentration, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60 ng.d/ml for vitaminD(2) and 204 for vitaminD(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1. VitaminD(2) potency is less than one third that of vitaminD(3). Physicians resorting to use of vitaminD(2) should beware of its markedly lower potency and shorter duration of action relative to vitaminD(3)

12 Trang, Vieth ea University of Toronto, Am J Clin Nutr.1998 . Evidence that vitaminD3 increases serum25-hydroxyvitaminD more efficiently than does vitaminD2. In all species tested, except humans, biological differences between vitamins D2 and D3 are accepted as fact. Subjects took 260 nmol (approximately 4000 IU)vitaminD2 (n=17) or vitaminD3 (n=55) daily for 14 d. With vitaminD3, mean (+/-SD) serum 25(OH)Dincreased from 41+/-18 nmol/L before to 65+/-17 nmol/L after treatment. With vitaminD2, the 25(OH)D concentration went from 434+/-18 nmol/L before to 57+/-13 nmol/L after. The increase in 25(OH)D with vitaminD3 was 23+/-16 nmol/L, or 1.7 times the increase obtained with vitaminD2 (14+/-11 nmol/L; P=0.03). There was an inverse relation between the increase in 25(OH)D and the initial 25(OH)D concentration. In the highest tertile [25(OH)D >49 nmol/L] the mean increase in 25(OH)D was 13.3 nmol/L (P < 0.03 for comparison with each lower tertile). Although the 1.7-times greater efficacy for vitaminD3 shown here may seem small, it is more than what others have shown for 25(OH)D increases when comparing 2-fold differences in vitaminD3 dose. The assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be reconsidered.

13. Hymøller L1, Jensen SK.Denmark J Dairy Sci. 2011;94:3462-6. Vitamin D₂ impairs utilization of vitamin D₃ in high-yielding dairy cows in a cross-over supplementation regimen. D(3) given after D(2) is less efficient at increasing the plasma status of 25(OH)D(3) than D(3) given without previous D(2) administration.

A Vitamin D Expert’s Take on the Latest Warning to Stay Out of the Sun to Avoid Skin Cancer

By Dr. Mercola 16/11/2014The US Surgeon General recently came out with a warning on skin cancer,1 claiming that the sun is dangerous and that you need to stay away out of it.

pioneer Dr. John Cannell, founder of the Vitamin D Council, has dedicated a large part of his professional career to the study of vitamin D and its health benefits, and he has a warning of his own to those who take this narrow-minded advice to heart.

It’s worth noting that the acting Surgeon General, Boris Lushniak, is a dermatologist. And of all the medical specialties out there, dermatologists are clearly the most biased against sun exposure, & as a result, against vitamin D.

This isn’t surprising, since they primarily see the ill effects of sun overexposure. But in taking an overly narrow view, the advice to avoid sun exposure as much as possible can have equally if not greater adverse health effects. The Connection Between Sun Exposure and Skin Cancer Unquestionably, UV radiation can be dangerous; it can increase your risk for certain skin cancers such as squamous cell, basal cell, and melanoma. But there are significant differences even between these cancers, and appropriate sun exposure may actually be more beneficial than detrimental in some cases. Dr. Cannell explains:

“Squamous cell carcinoma is clearly associated with chronic sun exposure. It is more common on the face, the hands, and the scalp.

It is related to radiation burden over your lifetime, and together with basal cell carcinoma, which is sort of intermediate, it accounts for approximately 1,500 deaths a year in the United States…

Basal cell is sort of intermediate. There are studies showing that it is associated with chronic sun exposure, and there are studies showing that it’s not associated with chronic sun exposure.

And then there’s melanoma, which is responsible for almost 9,000 deaths a year and is the deadly skin cancer that is feared. The relationship that melanoma has with the sun is quite complicated.

It is clearly associated with sunburn, especially sunburns when you’re young (that’s incontrovertible) or sunburns in a sun tanning bed.”

However, there are at least two studies showing that melanoma is more common in indoor workers than outdoor workers. And the most likely places for melanoma to appear are actually NOT the face and the hands like squamous cell carcinoma, but rather the lower back and the upper leg—areas that are usually not chronically sun-exposed.

According to Dr. Cannell, there’s a vocal minority in the dermatological community that thinks the emphasis dermatologists have on avoiding sun exposure is wrong, because while sunburn is a risk factor, chronic sun exposure is not.

“A number of studies show that chronic sun exposure is related to melanoma, but they don’t separate out the sunburns, which is very hard to do because you have to do that by memory,” Dr. Cannell says. Two Decades-Long Study Finds Sun Avoidance Doubles Risk of Death Dr. Cannell notes a recent study2 done in Sweden, which followed nearly 30,000 middle-aged to older women for up to 20 years. The average follow-up was 15 years.

At the outset, they asked a number of questions about sun exposure, such as: Do you sunbathe? Do you take vacations in sunny areas in the winter? Do you garden with short sleeves and shorts? And, do you use sunbeds?

What they found, and this appears to be the only study of this kind, is that the women who avoided the sun were twice as likely to die over the course of the study. The researchers attributed this finding to a vitamin D mechanism.

What this study actually shows is that chronic sun exposure appears to be associated with less mortality. It’s also the first study to show that women who use tanning beds live longer than those who don’t.

This is in direct conflict to what almost every dermatologist will say, including the Surgeon General. It’s unfortunate, but the danger of almost any specialist is that they don’t take the broader perspective.

What the Surgeon General and almost every other dermatologist fail to take into account is the overall mortality, which is referenced in this recent study. Risk-Benefit Analysis In addition to this study, dozens of others document the benefits of appropriate sun exposure. This includes a reduced risk of about 16 different cancers of Dr. Garland’s studies suggest this reduction is close to 50 percent.

So many hundreds of thousands of people are put at risk from other cancers as opposed to 10,000 people who are dying from skin cancer caused by sunburn. It’s really a matter of making an educated risk-benefit analysis.

“When you do a risk-benefit analysis and you look at all the data we have, the risk in my opinion appears to be in those who avoid the sun,” Dr. Cannell says.

“Now, if you avoid the sun, your risk for non-melanoma skin cancer goes down. That’s clear. But if you look at studies of either latitude or of 25-hydroxyvitamin D levels in relation to cancer, you find this inverse relationship: the higher the vitamin D level, the lower the internal cancer rate.”

Dr. William Grant of Sunlight, Nutrition, and Health Research Center (SUNARC) estimates that if everyone in the United States had a vitamin D level of 40 nanograms per milliliter (ng/ml), it would save approximately 150,000 lives a year.3

That’s 100 times the rate of squamous cell cancers, which are the only ones that are definitively linked to UV exposure. In Canada alone, it is estimated that 37,000 lives a year are lost due to vitamin D deficiency.4Also, use of sunscreen has risen in the last 30 years, so if dermatologists were correct, there should be a decrease in stage 1 melanoma. But there’s not. As sunscreen use increased, stage 1 melanoma diagnosis increased…

“It’s thought that by blocking out UVB, patients are able to stay out in the sun longer than they would have otherwise and expose themselves to the more dangerous, or at least potentially dangerous, UVA radiation that’s in the sunshine,” Dr. Cannell says. “What we recommend is what’s called safe, sensible sun exposures. The Australian Cancer Council now recommends the same thing. I think in England there’s now a change in their recommendation from strict sun avoidance to some safe, sensible sun exposure. There are some movements in large organizations to realize that safe, sensible sun exposure is a healthy thing.”

How Much Sun Exposure Is Sensible? On its website, Cancer Research UK reports that “by enjoying the sun safely and avoiding sunburn, people can reduce their risk of skin cancer and enjoy the beneficial effects of the sun.” Cancer Research UK’s sun advice is endorsed by the British Association of Dermatologists, Cancer Research UK, Diabetes UK, the Multiple Sclerosis Society, the National Heart Forum, the National Osteoporosis Society, and the Primary Care Dermatology Society. The UK National Health Service5 also recommends sensible, individualized sun exposure to help optimize vitamin D.

It’s important to recognize is how quickly sunlight can make vitamin D in the skin. You don’t need to be outside for hours on end. But you do need more than just a few minutes of sun on your face and arms. According to Dr. Cannell, sunbathing at solar noon in the summer, at most latitudes in the United States you will make between 5,000-10,000 international units (IUs) of vitamin D within 30 minutes.

“You can ask yourself why nature would evolve a mechanism that made so much vitamin D so quickly,” Dr. Cannell says. “When I thought about that question, the only answer I could come up with is nature did it for a good reason. The organism needs vitamin D, so the system in the skin evolved to make it very quickly upon exposure to sunlight.

We recommend full-body sun exposure for up to anywhere from a few minutes to 30 minutes every day. On those days when you cannot get a full-body sun exposure, we recommend a vitamin D supplement or sensible exposure in a low-pressure UVB bed.”

If you’re getting regular sun exposure, I think the need for an oral supplement is really minimal to non-existent. When you swallow a pill, there’s no self-regulating ability. Your body doesn’t have an ability to selectively limit its absorption. But your skin has the ability to control how much vitamin D is being produced based on how much is in your blood.

I personally have not taken oral vitamin D for five years and my level runs from 50-70 g/ml. Lifeguards, roofers, and gardeners who work with their shirt off, all tend to have levels between 40 and 80 ng/ml in the summer. This also brings up an interesting question about the difference between normal and natural. Normal vitamin D levels are an average of what indoor workers have in both winter and summer. Natural are levels of a population with widespread sun exposure. The latter is going to be closer to ideal, or optimal.

References for establishment of optimal levelsThere are also other reasons to strive for sun exposure rather than swallowing a pill. As noted by Dr. Cannell, aside from producing vitamin D, sunlight also affects nitric acid levels and endorphins in the skin. Researchers at the University of Wisconsin recently discovered that there may be a system at 311 nanometers that is separate from the vitamin D system (which is at 298 nanometers), and that there may be an entirely new undiscovered biochemical system in the skin that makes yet another substance, besides vitamin D. Time will tell what comes out of that research, but there are indications that sunlight may be responsible for other biological processes that are unrelated to vitamin D production.

Dr. Cannell’s Recommendation on Tanning Beds There are basically two
types of tanning beds:

1. High-pressure UVA beds. They tan you the quickest because it’s UVA that tans the skin. They contain only a limited UVB spectrum, and will therefore give you color but not much vitamin D

Low-pressure beds, which contain less UVB than sunlight at most latitudes, but still contain a significant amount of UVB. These are the beds Dr. Cannell recommends, provided you’re using a sensible approach that avoids sunburns. It’s important to realize that you can easily get burned after only a couple or a few minutes when using a tanning bed

Another important factor when selecting a tanning bed is the type of ballast it employs, to avoid excessive electromagnetic field (EMF) exposure. Most tanning units use magnetic ballasts to generate light. These magnetic ballasts are well known sources of EMF fields that can contribute to cancer. If you hear a loud buzzing noise while in a tanning bed, it has a magnetic ballast system. I strongly recommend you avoid magnetic ballast beds, and restrict your use of tanning beds to those that use electronic ballasts.

On days you cannot get either regular sun exposure or use of a tanning bed, Dr. Cannell suggests taking 5,000 IUs of vitamin D3. Other vitamin D experts recommend similar amounts. It’s worth noting that, according to the federal government’s Food and Nutrition Board (FNB), the no observed adverse effects level (NOAEL) of vitamin D is 10,000 IUs a day. This means there has never been a replicated reliable study showing that 10,000 units a day is in any way detrimental.

Many individuals who have reported side effects from taking high doses of oral vitamin D have noticed that when they supplemented with magnesium, they were able to tolerate the high oral doses of vitamin D. Dr. Carolyn Dean has written in her book, The Magnesium Miracle, that she has seen this so many times that she doesn’t advise taking more than 2,000 units of vitamin D without magnesium supplementation. Be sure to also have an adequate amount of vitamin K2 along with D to slow the progression of arterial calcification. Remember though that the best form of vitamin D is the one your body produces when it is exposed to sunlight that has sufficient amounts of UVB.

Five Tips to Get an Appropriate, Sensible Amount of Sun Again, sunshine offers substantial health benefits, including vitamin D production, but you do need to exercise a few simple precautions to protect yourself from overexposure. Virtually all of the harm from sun exposure is related to sunburn. Here are my top five tanning tips: * Expose large amounts of your skin (at least 40 percent of your body) to sunlight for short periods daily. Optimizing your vitamin D levels may reduce your risk of as many as 16 different types of cancer, including pancreatic, lung, ovarian, breast, prostate, and skin cancers. If using a sunscreen, give your body a chance to produce vitamin D before you apply it. *When you’ll be in the sun for longer periods, cover up with clothing, a hat, or shade (either natural or shade you create using an umbrella). *Consider the use of an “internal sunscreen” like astaxanthin to gain additional sun protection. Astaxanthin is a potent antioxidant (and pigment) produced by marine algae in response to their exposure to UV light. Typically, it takes several weeks of daily supplementation to saturate your body’s tissues enough to provide protection. *Consuming a healthy diet full of natural antioxidants is another useful strategy to help avoid sun damage. Fresh, raw, unprocessed vegetables and fruits deliver the nutrients that your body needs to maintain a healthy balance of omega-6 and omega-3 oils in your skin, which is your first line of defense against sunburn. Vegetables also provide your body with an abundance of powerful antioxidants that will help you fight the free radicals caused by sun damage that can lead to burns and cancer.

How Vitamin D Performance Testing Can Help Optimize Your Health A robust and growing body of research clearly shows that vitamin D is absolutely critical for good health and disease prevention. Vitamin D affects your DNA through vitamin D receptors (VDRs), which bind to specific locations of the human genome. Scientists have identified nearly 3,000 genes that are influenced by vitamin D levels, and vitamin D receptors have been found throughout the human body.

14 Oct 2014 update: MORE ON OPTIMAL VITAMIN D3 DOSE, AND THE DIFFICULTY OF ACHIEVING CLINICAL OVERDOSE: Four new reports highlight how difficult, and important it is to achieve adequate optimal bloodlevels of vitamin D with vigorous vitamin D3 supplements, let alone overdose with any significant adversity: note three used the recommended vitamin D3, not the long-condemned mislabeled Lennons/Aspen vitamin D2 (which is misleadingly labelled “caciferol” without disclosing that it is D2 not D3). Even a single 2 million iu overdose of vit D3 in nonagenarians had no adverse effect-since the bloodlevel was back to zero by 3 weeks, thats above 100 000iu/day on average….

van den Ouweland , Vollaard ea Nijmegen, The Netherlands in BMC Pharmacol Toxicol. 2014 Sep 30 describe Pharmacokinetics and safety issues of an accidental oral overdose of 2,000,000 IU of vitamin D3 in two nonagenarian nursing home patients: a case report. Oral overdose of 2,000,000 IU of vitamin D3 in two nonnagenarian nursing home patients was monitored from 1 hr up to 3 months . Peak blood 25(OH)D3 concentrations were observed 8 days after intake (210 and 162ng/mL, respectively (ref: 20-80 ng/mL), followed by a rapid decrease to undetectable levels after day 14. Remarkably, plasma calcium levels increased only slightly up to 2.68 and 2.73 mmol/L, respectively (ref: 2.20-2.65 mmol/L) between 1 and 14 days after intake,; phosphate and creatinine levels remained within reference range. No adverse clinical symptoms were noted. CONCLUSION:A single massive oral dose of 2,000,000 IU of vitamin D3 does not cause clinical toxicity requiring hospitalization. Toxicity in the long term cannot be excluded as annual doses of 500,000 IU of vitamin D3 for several years have shown an increase in the risk of fractures. This means that plasma calcium levels may not be a sensitive measure of vitamin D toxicity in the long term in the case of a single high overdose.

As previously reported, to avoid dehydration stones and vascular calcification – especially in hot dry climates – , the precautions with vigorous vit D3 are to add some vit K2 and magnesium to the supplement, and maintain good water intake .

The fourth current paper, from Morocco, reports inexplicable use of dangerous massive dose of vit D2 in neonates- amounting to about 120 000iu/kg ie about 12 times the maximum adult dose reported : Hmami , Bouharrou ea Morocco University, Arch Pediatr. 2014 Oct;21:1115-9. [Overdose or hypersensitivity to vitamin DVitamin D intoxication with severe hypercalcemia is rare in the neonatal and infancy period. 9 babies between ages of 25 and 105 days were admitted for treatment of severe dehydration 8 to 15% with hypercalcemia, with preserved diuresis and loss weight between 100 and 1100 gm secondary to taking 600,000 units of vitamin D (Sterogyl(®). The pregnancies & deliveries were normal. Clinical signs were dominated by weight loss, vomiting, and fever. The vitamin D values in nine patients were toxic (mean 220: 139 – 300 ng/mL, ; normal >20ng/mL; toxicity if >100ng/mL). Nephrocalcinosis was shown in seven patients. DNA study in eight patients, did not reveal a mutation of the vitamin D 24-hydroxylase gene (CYP24A1). Treatment consisted of intravenous rehydration with diuretics and corticosteroids. Serum calcium returned to normal range within 4-50 days, with weight gain progressively over the following weeks. The follow-up (2 years for the oldest case) showed persistence of nephrocalcinosis. Genetic susceptibility and metabolic differences appear to modulate the threshold of vitamin D toxicity. However, respect for recommended doses, recognized as safe in a large study population, reduces the risk of toxicity.

VITAMIN D3 DOSE:We get excellent results in outpatient adults with loading oral dose of vit D3 of about 200 000 to 400 000iu depending on illness severity and body mass; then pro rata about 50 000iu per week till better, tapering to fortnightly when well; pro rata in kids. We monitor calcium and 25OH vitamin D3 levels occasionally if affordable – but with the tapering regime, and published data, do not see or expect hypercalcemic problems from a mean conservative weekly maintenance dose of about 3500iu/d longterm, with predicted bloodlevel of 25OHvitD of about 35-40ng/ml. As a senior with average chronic dis-ease load, I take ~63 000iu vit D3 weekly, but double it occasionally if I do get a bad cold; so I never miss a day’s work; recent stress-related shingles (2nd attack in 30 years) was just a nuisance, settled in 3 weeks with this regime plus multigrams of buffered vit C a day; oral lysine and alphalipoic acid each about 1/2 gm/day; and for a few days some weak steroid and humic acid cream topically for the neuritis and blistering, which has already healed to almost invisible. This week at a family practice clinic I saw two successive women with shingles – now a frequent occurrence, even without HIV…

Khan in Toronto in OHDM this September describes a ~60yr old man with tongue cancer who was treated inter alia with Vit D3 10 000iu a day; after a year his 25oH vitD level was ~106ng/ml, when his dose was halved; his dose response bore out the general experience that at average adult mass, vit D level rises by about 10ng/ml for every 1000iu vit D3 per day or pro rata dose weekly etc eg 50 000iu/wk or 100 000iu fortnightly may give average vit D level of ~70ng/ml. .

Singh & Bonham 2014 at Kansas University describe A Predictive Equation to Guide Vitamin D Replacement Dose in Patients. “The recommended daily allowance for vitamin D is grossly inadequate for correcting low serum concentrations of 25-hydroxyvitamin D in many adult patients. In their population (average BMI 31.5) ,about 5000 IU vitamin D3/day is usually needed to correct deficiency, and the maintenance dose should be ≥2000 IU/day. The required dose may be calculated from the predictive equations specific for ambulatory and nursing home patients” A BMI of 31.5kg at a mean height of about 1.7m gives a mean weight of 91kg, which at the consensus daily vit D3 dose of 80iu/kg/d totals ~7100iu/d or 50 000iu/wk- perhaps a reasonable maintenance dose for winter, half that in summer if reasonable weekly sun exposure. .

29 Sept 2014: As detailed elsewhere in this column, there is at least 70 years of strong experience worldwide that all microorganism infections are greatly diminished by natural prevention (not synthetic vaccines loaded with toxic heavy metals and allergenics eg egg) , and easily treated ie thrown off, with vigorous immune-boosting supplements: (mega)grams a day of vitamin C or as kgs/day of fresh produce; vitamin D3 80+ iu/kg/d to >10 000iu/d ie 300 000 to 600 000iu loading dose; then +-50 000iu/wk, plus plenty of skin exposure to sunshine; iodine; zinc; selenium; silver; the other vitamins; Ecchinacea etc. This applies both to acute and chronic infections and degenerative conditions.

To be used in highrisk cases eg MERS, AIDS, ebola etc: The landmark trial Effect of High-Dose Vitamin D3 on Hospital Length of Stay in Critically Ill Patients With Vitamin D Deficiency– The VITdAL-ICU Randomized Clinical Trial by Amrein, Dobnig ea , published today in JAMA from Austrian hospitals is most encouraging about the immense value of vigorous dose and bloodlevels of vitamin D3 against all types of severe disease. The dose used in this trial (loading dose 540 000iu =~18000iu/d 1st month, but averaging only ~8000iu/d in the first 3mo) did not achieve vigorous vit D bloodlevel, presumably because the loading dose of vit D3 in oil (540 000iu) was given by tube into the stomachs of critically ill patients; it would have better been given by transdermal injection, or else a much higher loading gastric dose given so as to speedily achieve a bloodlevel of around 70 (60 to 80) instead of half of this that was achieved in the crucial first few weeks . “from May 2010 through September 2012 at 5 ICUs the trial recruited 492 medical (60%) and surgical (40%) critically ill adult white patients , 35% women, BMI mean 27, mean age 64.6 years (SD, 14.7) with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3540 000 IU, or placebo given orally or via nasogastric tube; ; followed by monthly maintenance doses of 90 000 IU for 5 months- ie= about 18000iu/day for the first mo, then 90 000iu mthly ie only 3000iu/d. . RESULT: on placebo the 25hydroxyvit D3 level doubled from 13 at baseline to 17 at a month to 26ng/ml at 6mo.. By contrast, on vit D3 supplement it doubled to 34 at days 3 and 7 and day 28, but up to 46 at 6 months ie only 80% higher than the control group – thus 1/3 to 1/2 of the optimal target; with this, where 100% of patients were below 25OHvitD at baseline ie on admission to ICU, by 7 days, 87% were still in this bracket and none above 60ng/ml on placebo vs 25% below 20 and 13% above 60 on vit D3; and by 6mo 35% were still that low on placebo, vs 5% at that low, but 22% above 60 on vit D3.So it is not surprising thatMedian hospital stay 20 days was not significantly different between groups Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28% for vitamin D3 vs 35% for placebo; hazard ratio [HR], 0.81 P = .18; 6-month mortality: 35.0% for vitamin D3 vs 42.9% for placebo; HR 0.78 P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 19.5 days. Hospital mortality was significantly 40% lower with 28 deaths among 98 patients (28.6% ) for vitamin D3 compared with 47 deaths among 102 patients (46.1% ) for placebo (HR, 0.56 P for interaction = .04), but not 6-month mortality (34.7%] for vitamin D3 vs 50.0% for placebo- ie 31% lower; HR, 0.60, P for interaction = .12). No serious adverse events were observed. The highest 25-hydroxyvitamin D levels measured were 107 ng/mL on day 7 and 106 ng/mL at month 6- well below the theoretical minimum toxic threshold of 150 or 250ng/ml..”

As Salahuddin ea note, the good results in Pakistan in only 3 months with vigorous INITIAL dose vit D3 contrasts with Two recently published large randomised, controlled trials of conservative vitamin D3 over months that achieved far lower blood vitamin D levels found no difference in clinical outcomes or mortality after 400,000IU of 25-hydroxyvitamin D3 or placebo were given by Martineau ea in London, UK to 146 pulmonary TB patients – where mean (trough or midpoint) vit D level (after 100 000iu vitamin D(3) or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment) – was surprisingly only 40ng/ml at 56days – ie after a mean of 7000iu/d by 56 days, vs 10ng/ml on placebo)- less than half of the bloodlevel achieved on vit D3 in the Pakistan trial.

So the Austrian ICU patients would undoubtedly have done much better if given more effective (ie in critically ill pts intramuscularly imi or subcutaneously) loading dose like the Salhuddin trial did.

TIME To SWOP FROM MISNAMED “STRONG CALCIFEROL” VIT D2 TO THE REAL VIT D3: as the winter solstice approaches here, with fierce weather linking to the expected influenza-like outbreak (while the MERS-CoV outbreak abates with summer in the severely vitamin D deficient Saudi Arabians), a new major study shows the supremacy of vitamin D3 for supplementation, and confirms that vitamin D2 benefit if any is so mediocre as to be unethical..

Its sad that despite the strong evidence against using vitamin D2 supplement discussed last year, it seems no one acted on it despite the confirmatory paper from Bergen of last September.

Thus vit D3 is again confirmed as four times as potent as D2. But crucially, that giving vit D2 may actually SUPPRESS the optimal serum vit D3 level.

We health professionals with our highly vulnerable populations in South Africa and worldwide (epidemic/endemic HIV, TB, cancer, drug addiction, MERS-CoV, asthma, diabetes, cardiovascular, malnutrition, alcoholism and violence) therefore surely have no choice but to swop promptly from prescribing vit D2 “Strong Calciferol” (a dangerous misnomer) to prescribing vitamin D3 at vigorous dose (with if possible occasional blood level check of 25OHvit D3)- at a trivial imported and distributed cost (100cws) to South African state clinics of perhaps<1/4 of the cost of D2 eg R1 per patient per month for a conservative 100 000iu monthly (ie after an appropriate germicidal loading dose of eg 3000 iu/kg) if not the more realistic dose double that- still at only eg US$0.2 a month.

Health Authorities everywhere have an obligation to enforce the use of vitamin D3 and not vitamin D2 globally ..

update 3 Sept 2014: while the MERS outbreak in Arabia may at last be dying down, real highly infections plagues eg ebola malaria cholera typhoid, MRSA, TB and HIV etc continue rampant, maiming and killing even more than the manmade wars raging on some continents. .

So it is ironic – or typical of the couldnt-care-less greedy politicians and potentates who run the world- that the medical authorities they employ worldwide apparently continue to ignore the dramatic benefits of at least safe antimicrobial supplements like multivite, zinc, iodine, selenium, and especially vigorous dose vitamin D3 at negligible cost, and highdose buffered vitamin C to tolerance, and colloidal silver.

We quote above trials and evidence that oral vit D2 may be actually harmful, that it is vit D3 in vigorous dose that is needed to at least treble if not quadruple the blood vit D level from the usual deficient levels we find, to between 60 and 100ng/ml during illness. Unfortunately locally this is not only not grasped, but also the vit D assay kit being used by private laboratories measures only total 25OHvit D level, not the needed active 25OH vit D3 level plus the potentially harmful (vitD receptor-blocking ) 25OHvit D2. This is a crucial omission which has been corrected by eg the Mayo Clini Lab, which routinely reports both D3 and D2 levels.

In the person not on vit D supplements, the mediocre ie insufficient total vit D level may mask that the crucial vit D3 level is actually seriously low- deficient. In the person on vigorous vit D2 supplement (the spuriously named “strong calciferol” 50 000iu tab no longer prescribed in USA but commonly in RSA, that neglects to state it is D2 not D3), the total 25OH vit D assay will be even more misleading if the level is well up, without the unwary being informed that it is harmful D2 that is elevated, and blocking the needed vit D3 level that the D2 is suppressing.

15 June 2014 CRUCIAL EFFECTIVE VITAMIN D3 DOSING: A major new metaanalysis of the benefit ofVitamin D3 and RespiratoryTractInfections RTIin PLOS 2013 at Sweden’s Karolinska Institute Bergman ea showed that in the 11 relevant trials (published between 2007 and 2012 ie done through the first decade of this century) using vit D3, “Overall, vitamin D showed a protective effect against RTI (OR, 0.64; 95% CI, 0.49 to 0.84). And the average vit D level at baseline was only 24ng/ml, but with the mediocre vit D3 doses used then of average 2000iu/d (300 – 4000iu/day) given for between 7wks and 3 yrs, the average bloodlevel achieved on replacement was only 50% higher at 36ng/ml”.

This confirms more direct experience with higher doses that blood level increment, and benefit, is proportionate to vit D3 dose, at least up to the proven speculative safe upper dose of at least 10 000iu/day (whereas the proven safe longterm daily dose is up to 50 000iu/day). “More important, the protective effect was larger in studies using once-daily dosing compared to eg monthly bolus doses (OR=0.51 vs OR=0.86, p=0.01)”. This concurs with our experience of major benefit against respiratory infection that is based on published studies giving a loading month’s dose of about 80-100 iu/kg/day ie ~3000iu/kg; then that monthly dose split conservatively eg 50 000iu every week or two depending on mass, and severity of ill-health; to a more successful blood-level of 60 to 100ng/ml.

These recent studies force us to conclude that bad weather, and bad prevalent respiratory viruses, and especially with major acute, or chronic illness as in those with or at risk of serious infections eg major trauma or sepsis, MERS-CoV, Ebola, malaria, cholera, cancer, diabetics, smokers, asthmatics, bronchitics, AIDS-TB., pneumonia and old age sufferers, and especially hospital, laboratory and clinic- health workers- we should give a loading dose of about 4000iu/kg, then 10 000 iu/d for an average 70kg adult, or 50 000iu every 5 days, or more simply 75000iu (about 1.5ml of 100cws vit D3 powder) weekly; or at a stretch, 300000 if not 400 000iu monthly. . As the common imported powder concentrate is 100 000 iu / Gm ie per 2 ml, it is simple to take the slightly sweetish powder up to 2 or more 4 ml teaspoons ie 200 000 -400 000 iu on the tongue.

The majority of residents of developed countries now live urbanised with mechanized transport, do not live and work / walk all day stripped in the sun. The poor malnourished peasants live crowded in ghettoes , and the poorest are generally the darkest skinned and therefore make the least vitamin D3. So with rare exceptions, everyone needs the vigorous vitamin D 3 doses discussed above.

But at the prevalent bulk vit D3 powder price of at most about $0,o2 per 100 ooo iu, at a mean population age of around 20 to 25 yrs -outside Europe- it would cost a country of eg 50 million people perhaps $o.5 per head per year ie conservatively $25 million a year to prevent > 90% of common illnesses including drugging and violence consequences. Of course no government can tolerate such massive loss of jobs and taxes in a decimated disease industry that turns over $ trillions annually – up to 18 % of national budgets. So it’s up to individual adults, especially householders, educators and employees , to see that the cheapest cure- all after clean water – vitamin D3 – is recommended and freely available.

We health professionals with our highly vulnerable populations in South Africa and worldwide (epidemic/endemic HIV, TB, cancer, drug addiction, MERS-CoV, asthma, diabetes, cardiovascular, malnutrition, alcoholism and violence) therefore surely have no choice but to swop promptly from prescribing vit D2 “Strong Calciferol” (a dangerous misnomer) to prescribing vitamin D3 at vigorous dose (with if possible occasional blood level check of 25OHvit D3)- at a trivial imported and distributed cost (100cws) to South African state clinics of perhaps<1/4 of the cost of D2 eg R1 per patient per month for a conservative 100 000iu monthly (ie after an appropriate germicidal loading dose of eg 3000 iu/kg) if not the more realistic dose double that- still at only eg US$0.2 a month.

Health Authorities everywhere have an obligation to enforce the use of vitamin D3 and not vitamin D2 globally ..

Queries and rebuttals all over the world are questioning the negative French (Autier ea) Vitamin D status and ill health: a systematic review published last month by the UK Lancet Low serum concentrations of 25-hydroxyvitamin D (25[OH]D) have been associated with many non-skeletal disorders. However, whether low 25(OH)D is the cause or result of ill health is not known. We did a systematic search of prospective and intervention studies that assessed the effect of 25(OH)D concentrations on non-skeletal health outcomes in individuals aged 18 years or older. We identified 290 prospective cohort studies (279 on disease occurrence or mortality, and 11 on cancer characteristics or survival), and 172 randomised trials of major health outcomes and of physiological parameters related to disease risk or inflammatory status. Investigators of most prospective studies reported moderate to strong inverse associations between 25(OH)D concentrations and cardiovascular diseases, serum lipid concentrations, inflammation, glucose metabolism disorders, weight gain, infectious diseases, multiple sclerosis, mood disorders, declining cognitive function, impaired physical functioning, and all-cause mortality. High 25(OH)D concentrations were not associated with a lower risk of cancer, except colorectal cancer. Results from intervention studies did not show an effect of vitamin D supplementation on disease occurrence, including colorectal cancer. In 34 intervention studies including 2805 individuals with mean 25(OH)D concentration lower than 50 nmol/L at baseline supplementation with 50 μg per day or more did not show better results. Supplementation in elderly people (mainly women) with 20 μg vitamin D per day seemed to slightly reduce all-cause mortality. The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status is reported in a wide range of disorders. In elderly people, restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival.

Ongoing randomised clinical trials assessing the ability of vitamin D supplementation to reduce the risk of several non-skeletal disorders involve a population larger than that of Cambridge, UK, and will cost millions of research dollars. VITAL, for example, will enroll 20 000 participants and has US$22 million in funding. This vast investment of effort by patients, researchers, and funders is laudable, as it is almost certain that it will be sufficient to answer a question that has long kept the medical community in the dark.

Vitamin D first became a medical success story when its importance in bone health and calcium homoeostasis was proven decades ago. Since then, epidemiological evidence has been accumulating to support a role for vitamin D in the protection of individuals from various non-skeletal disorders including cancer, cardiovascular diseases, autoimmune and inflammatory diseases, dementia, and diabetes; it might also reduce all- cause mortality. Many of these studies show a strong association between low vitamin D concentrations anddisease. However, the results of myriad recent small randomised controlled trials are almost unanimous in concluding that vitamin D supplementation provides protection from few, if any, of these outcomes.

Vitamin D is a steroid hormone with pleiotropic and tissue-specific effects owing to the wide expression of the nuclear vitamin D receptor in many different tissues,and the many genes that are targeted by its actions. In the skeletal system, vitamin D promotes healthy development and remodelling of bone. In other tissues, vitamin D is postulated to mediate potentially beneficial effects via a wide variety of mechanisms: some evidence suggests that it exerts anticancer activity by limiting hyperproliferation of certain cell types, that it promotesmetabolic health by regulating lipid metabolism in adipocytes, and that it limits autoimmunity bysuppressing inappropriate immune responses. In a systematic review in The Lancet Diabetes & Endocrinology editorial , Philippe Autier and colleagues discuss a large number of observational studies suggesting That high serum concentrations of vitamin D might be protective.

For example, those with high vitamin D had decreased risk of cardiovascular events by up to 58%), diabetes (by up to 38%), colorectal cancer (by up to 33%), and all-cause mortality (by up to 29%). However, they also compare these findings with the results of randomised clinical trials, which reveal a very different picture: no reduction in risk was found, even in trials involving adequate supplementation of participants with lowvitamin D levels at baseline (less than 50 nmol/L). Autier and colleagues also did a new meta-analysis of 16 trials that assessed the effects of vitamin D supplementation on blood HbA1c, a biomarker mainly used for monitoring disorders of glucose metabolism.

Although type 2 diabetes is associated with low vitamin D, the results show that vitamin D supplementation does not reduce HbA1c

. Thus, it looks increasingly likely that low vitamin D is not a cause but a consequence of ill health.

Despite the growing body of evidence indicating that vitamin D is unlikely to prevent non-skeletal disorders, there is strong support for its use from many prominent members of the research community, which is fuelled by the relatively low toxicity of vitamin D, the glimmer of positivity from some trials,and the large body of evidence from prospective observational studies. For those who ‘believe’, the lack of benefi t found in most trials completed thus far can be attributed to issues including inadequate supplementation, testing of a population not sufficiently vitamin D deficient at baseline, incorrect

formulation, underpowering, or insufficient follow-up. Vitamin D might not be safe in all settings, however.

Supplementing at high doses could cause harm in people with already high concentrations of serum vitamin D, particularly in those with liver, kidney, or vascular problems. This is a concern, given the large number of people taking vitamin D supplements (up to 50% of adults in the USA).

Large clinical trials to assess the effects of vitamin D on non-skeletal health outcomes are therefore justified. It would be a real boon to patients if the results are positive, but unless effect sizes for clinically important outcomes are large, the results will only confirm the neutral effect reported by most clinical trials thus far. Although this investment might therefore have little effect on current guidelines, the results will at least allow the research community to move on.

This French review of Vitamin D is the sort of tactic regularly concocted by Big Pharma and the Disease Industry for the media, to discourage patients and doctors from taking/prescribing effective doses of supplements (beyond a lowdose multivite a day), instead force them to take Big Pharma poisons- synthetic new risky designer drugs- like antibiotics, antipain, anticancer, anticholesterol, antiosteoporosis, antiplatelet,antihypertensive, vaccines, antiflu, – to make massive profits for the Disease Industry, but not address or cure the deficiency causes of disease. At the behest of Big Pharma like Roche, their lobbyists the FDA, the European Medicines Authority and the UK NHS are trying to push through legislation that will make anything but lowdose multisupplements available to the public solely on doctors’ prescription.

Meanwhile, Big Pharma companies are paying fines of over $10 billion a year for promoting their snakeoil prescription designer drugs by fraud, when these drugs are allowed to be registered for chronic use after small trials of only 6 to 12 weeks, and the researchers who publish the trials for megadollar fees are regularly caught out, fired but rarely jailed. …… The Big Pharma guys simply bill the cost of the fines into their marketing expenses- their bosses, and the politicians they buy off, are too big to jail… Regulators then allow the drugs to be prescribed for years until enough patients sicken and die for there to be an uproar and cancellation- as happened recently with Prot(e)os the synthetic ranelate ‘osteoporosis’ snakeoil;. Now a top Dutch researcher has been fired for falsifying trials to promote betablockers for hypertension – when these have been discredited as routine therapy for this purpose for over a decade.

yet the Regulators led by the FDA – which is massively funded solely by Big Pharma as their ally- insists that vitamins, minerals and other long-proven natural supplement therapeutics, prime human hormones like melatonin and physiological human sexhormone creams , have to undergo $multimillion trials before they can be marketed as already long-evident safe effective therapies.

none of the vit D trials used the dose of vit D3 now recommended on solid evidence that we should all take – 80 (to 100)iu/kg/day or 2400-3000iu/kg/month of vitamin D3- ie about 150 000 – 200 000 iu to start and then per month for average adults – to maintain healthy 25OH vit D levels around 60-100ng/m (here our bloodlevels are usually between 10 and 20 ! because we take little dairy products, nuts and sunshine- we cover up and live indoors.) .

Most of the reported trials used only about 5% of the recommended vit D dose ie ~200 to 400iu/day ie 6 iu/kg/day! this dose does nothing except partly prevent rickets- in infants! Pregnant women are still routinely given such weak near-nonsensical doses of vit D.

and as Cannell’s review of the Autier analysis points out, the vitamin D trials trials under way – * in USA-Boston VITAL study 20 000pts) , Finland (FIND 18000 pts and UK(VIDAL1600pts ) , in some 40 000 subjects, due for publication only between 2017-2020- are using only 1600 to 3200iu vit D a day or about 48 000 to 96000iu/month ie perhaps 32iu (25 to 40) /kg/day. So they are testing still modest doses and blood level targets. .

ideally you should check your 25OH vit D and calcium levels to make sure you are on the right dose- but always taking some magnesia supplement, and at least 2 liter of water/ sodawater/clear fluid a day to avoid dehydration, kidney stones and vascular disease (which highdose calcium supplement eg 1000mg & vit D3 400iu/day cause).

8 April 2013 UPDATE: VITAMIN D3 THE AMAZING SUPPLEMENT

It is sad to record that Dr Walter Stumpf died suddenly a few months ago during ongoing correspondence. The world has lost a teacher of the century in both biological sciences and the humanities, metaphysics and philosophy,..

This week – as flu mushrooms in the southern hemisphere autumn- the Canadian Medical Association Journal April 3-8 features early-release articles on concerns about the Asian flu viruses and especially the SARS-nCorVirus. Is mass vaccination the answer? or did this in fact worsen mortality in previous North American epidemics of eg H1N1? which brings us back to global protection against infections and all major diseases with lowcost safe VitaminD3 at say 50 000iu(~700iu/kg)/week plus the other all-system protective supplements – eg multivitamins (especially vit C and K) and minerals especially magnesium, zinc, idine and selenium; and during epidemic times, major daily boost in vits D3 and C.

In December 2012 the University of San Diego published a useful researched update on vitamin D3 and breast cancer; pointing out again that while the increase in benefit obviously drops off with increasing dose, safe dose is up to at least 10 000iu a day or 70 000iu a week, to a bloodlevel around 100ng/ml; and toxic dose requires at least 40 000 iu a day chronically (if not 600 000iu/d as other evidence suggests). The projections for breast cancer reduction fit with the same team’s predictions in 2007.

So apart from maintaining good water intake, and avoiding taking ill-advised unbalanced solo calcium supplement, for optimal dosing in those with cancer or any other high risk, blood levels of both 25hydroxy vit D3, 1,25 calciferol, calcium, phosphate and creatinine, should be monitored occasionally, to avoid the rare risk of kidney stones and arterial/breast calcinosis.

Remember that magnesia, phosphate and vitamin C and K2 supplements are amongst the most important of at least 40 to accompany vitamin D3.

Last month three new studies affirmed the importance of vigorous vitamin D3 levels for genetic, heart and all health.

Holick’s group at Boston University show the profound .Influence of vitamin d status and vitamin d3 supplementation on genome wide expression of white blood cells. No studies have reported on how vitamin D status and vitamin D3 supplementation affects broad gene expression in humans. A randomized, double-blind, single center pilot trial was conducted for comparing vitamin D supplementation with either 400 IUs (n = 3) or 2000 IUs (n = 5) vitamin D3 daily for 2 months on broad gene expression in the white blood cells collected from 8 healthy adults. in the winter. CONCLUSION SIGNIFICANCE: Our data suggest that any improvement in vitamin D status will significantly affect expression of genes that have a wide variety of biologic functions of more than 160 pathways linked to cancer, autoimmune disorders and cardiovascular disease with have been associated with vitamin D deficiency. This study reveals for the first time molecular finger prints that help explain the nonskeletal health benefits of vitamin D

The magnitude of vitamin D inputs in individuals not taking supplements is unknown.. they reanalyzed 3000 subjects’ individual 25(OH)D concentration data from 8 studies involving vitD3 supplement. The total basal input (food plus solar) was calculated to range from a low of 778 iu/d in patients with end-stage renal disease to a high of 2667 iu/d in healthy Caucasian adults. Consistent with expectations, obese individuals had lower baseline, unsupplemented 25(OH)D concentrations and a smaller response to supplements. Similarly, African Americans had both lower baseline concentrations and lower calculated basal, all-source inputs. Seasonal oscillation in 4 studies ranged from 5.20 to 11.4 nmol/L, reflecting a mean cutaneous synthesis of cholecalciferol ranging from 209 to 651 iu/d at the summer peak. We conclude that: 1) all-source, basal vitamin D inputs are approximately an order of magnitude higher than can be explained by traditional food sources; 2) cutaneous, solar input in these cohorts accounts for only 10-25% of unsupplemented input at the summer peak; and 3) the remainder must come from undocumented food sources, possibly in part as preformed 25(OH).

August 2009 SUMMARY: Evidence is overwhelming that the prime sun-induced steroid hormone Vitamin D3 cholecalciferol – soltriol- is invaluable in 20fold higher dose ie perhaps 5000 to 10 000iu/day rather than has been preached to date (200- 400iu/d), as part of lifelong hormone replacement HRT to prevent all major chronic degenerative diseases in all humans living and working indoors. Effective dose of vitamin D3 supplement can reduce deathrate and disease by an astonishing 20%- that is indeed a panacea almost as good as other natural micronutrient supplements eg fish oil, metformin, and appropriate sex hormone replacement SHRT. It is becoming clear that with rare exceptions everyone- especially those with serious disease eg cancer, heart, lung, brain, nerve/muscle/bone/joint or inflammatory bowel diseases or chronic infections like TB HIV influenza or human papilloma virus – should take a daily supplement of about 10 000iu (1/4 mg) vitamin D for as little as ~ R10 US$1 a month ; ideally under supervision of some health professional. All that is required is occasional check of blood chemistry, and good diet and fluid intake.

And obviously because of vitamin D3’s benefits in lowering all diseases, when using vigorous dose vitamin D, one must expect to need to lower prescription drug treatments for diabetes, hypertension, depression, heart disease, lung disease, arthritis, infections etc as these ailments improve from the vitamin D replacement over months.

This review is especially appropriate on our Womens’ Day 9 August 2009 for a natural product so important for the health of women , that commemorates the year 1956 when 20 000 women marched in defiance of male despots’ fascist apartheid pass laws. The ages-old discrimination against women is epitomized by the pragmatic liberal economist Professor Ken Galbraith’s lecture to the Royal Society of Medicine in 1973 on the problem of unequal development and centralization of power in male technostructure – profit maximization.

No-where in business is this better shown than in Big Business creating demand by saturation marketing, including the medicalization of health. This involves disease-mongering through creating unnecessary concerns so as to expand markets among the well for patents eg blanket cholesterol or mammography or colonoscopy screening, or remedies for eg female arousal disorder, anxiety, reactive depression, mild-to-moderate hypercholesterolemia – when very few have been proven to need or benefit from such labels, procedures and drugs.

VITAMIN D3 SOLTRIOL : INFORMATION EXPLOSION:

The first of 46200 entries on Medline on vitamin D is from Oxford by Heaton 1922 . There are 272 500 entries on vitamins since 1918, the first specific one by Jack Drummond in 192o, but of course vitamin D was first identified by Mellanby 1919, preceded by vits A, B1 and C between 1909 and 1912. From a recent historical review (table 1) of hormones, vitamin D3 was perhaps the 7th hormone recognized after testosterone and estrogen (China 2600 years ago) , thyroid (1891) epinephrine secretin parathyroid and antidiuretic hormone.

Soltriolis an exquisite description for a sun-activated steroid, the cardinal prohormone vitamin D3 made from cholesterol via sunlight exposure. Soltriol is not in a 1964 Oxford Dictionary, nor is it’s etymology detectable on Google search; it was indeed invented by the pioneer polymath neurologist Dr Walter Stumpf . On Medline search for soltriol, the first result is Corradino 1973…

It is intriguing to read that Dr Stumpf graduated in medicine in 1952- and 50 years later in 2005 he wrote on his website: “From the microautoradiographic target recognition and related actions it follows that vitamin D has healing potential for prevention and treatment of various deficiencies and ailments, including old age: a PANACEA? If there is any compound that deserves being designated a panacea, the multifunctional heliogenic vitamin D appears a suitable candidate. Philosophical consideration: “Vitamin D”, the term does not reflect its significance. I have used instead SOLTRIOL in several publications as a more appropriate designation. – Is there not a link to Heraclitus emanation of “ ever-living fire ”? The cosmic solar fire (Soltriol) as the sustaining life force, providing wave length energies for Temperature, Visible Light , and Ultraviolet B “. ” The Main Biological Role of Vitamin D is Seasonal Adjustment of Vital Functions: These include regulation of growth, reproduction, survival stress response; endocrine and exocrine secretion, cell proliferation, cognition and mood; neuro-motor, neuro-endocrine, and neuro-sensory functions, immune response, cardio-vascular and gastro-intestinal functions, regulation of calcium and other mineral levels, cell proliferation and protein synthesis-differentiation.

Considering the decades of vitamin D use for its other benefits, it is ironic that a 1999 University California website on The History of Vitamin D has never been updated to cover more than the anti-rickets protection from vitamin D. But as Prof Stumpf writes to me today, ultimately it is the sun that is the panacea, transmitting it’s healing powers via the skin-activated messenger hormone vitamin D.

It is now almost a year since this column last reviewed vitamin D3’s benefits against all major diseases (see table) – during which year scores of new randomized controlled trials RCTs of vitamin D have appeared- there are now some 1680 RCTs on it since 1965. Carpenter 1999 reviews Forgotten Mysteries in the History of Vitamin D.

Women have a raw deal: due to their prime role and innate sense for survival of the species, for nuturing and caring, they live about 10% longer than their mates, but as a result endure far more illness, as well as assault, disability and murder (mostly inflicted by the careless male).

PROTEAN STEROIDS, PROTEAN FUNCTIONS: Calcitriol is one of many human steroids that include the sex hormones, aldosterne and digoxin; as well as nonhuman steroids which also have important medicinal use- like phytosteroids, equine steroids like the equilins eg premarin, and the important ecdysteroids in insects and some plants. Stumpf has again stressed the wide distribution in humans of vitamin D receptors VDRs, indicating their importance in protean human functions far beyond calcium regulation.

VITAMIN D AND ALL-CAUSE MORTALITY:it is just a year since Melamed ea from USA showed that having low vitamin D (as opposed to high level) increases all-cause mortality by 26%- thus taking submaximum safe dose of vitamin D can improve chance of survival by about 20%. This for as little as R10/month – $1- in South Africa.

In 2000, the Seven Country Study Group showed that ” saturated fat,vitamin C and smoking are the major determinants of all-causemortality at the population level” ie the higher the fat and smoking intake and the lower the vitamin C, the higher the deathrate. We now know better- serious vitamin D deficiency joins the list, which of course includes alcoholism. .

VITAMIN D AND CARDIOVASCULAR DISEASE CVD

Pizzorno 2009 reviews the strong evidence of the importance of balanced vitamins A D and K supplements in reversing the epidemics of both CVD and osteoporosis.

VITAMIN D AND DEPRESSIVE/NEURODEGENERATIVE DISEASE

over 20 articles already this year attest to the importance of vigorous vitamin D levels in reducing these diseases.

The much higher incidence of autoimmune diseases in women – especially SLE systemic lupus erythematosis and RA rheumatoid arthritis- let alone far higher younger female risk for fractures- must have been obvious for millennia. So obviously genetic female factors play a major role in these diseases – now surely attributable largely to the reproductively necessary absence of the Y chromosome, and thus the 100fold lower testosterone: estradiol T:E2 ratio in women (perhaps 2:1) than in men (in youth, >200:1).. It is common cause that estrogen is immunostimulant whereas testosterone and progesterone (like vitamin D) are immunomodulating. Hence testosterone and progesterone levels soar during pregnancy to prevent the mother rejecting her foetus. This partly also explains why vigorous vitamin D supplement also greatly improves fertility and pregnancy outcome.

VITAMIN D AND RHEUMATOID ARTHRITIS: many studies show the benefits of the prime anabolic steroids- vitamin D and androgen (Devis 1950) supplements- in treatment of all inflammatory disease, especially when inflammation itself weakens bone and all other tissues. The latest – last month (Chabchoub 2009)- shows “a possible role for XCI mosaicism in the pathogenesis of RA and thyroid disease and may in part explain the female preponderance of these diseases”. But the first and only randomized controlled trial of the effect of vitamin D on modifying RA appears in 1973 (Brohult) and the only open trial (Andjelkovic 1999) in RA showed that “alphacalcidiol is a powerful immunomodulatory agent with fairly low hypercalcemic activity”.

VITAMIN D INTOXICATION: The low toxicity of vitamin D3 is fortunate because while it is ideal to monitor vitamin D levels on effective replacement, the blood test costs about R660- $80- locally; hence all one needs to do is exclude kidney problems (which may need even higher dose of vitamin D3), and risk of kidney stones- but perhaps checking blood calcium and creatinine at baseline and occasionally, and ensuring balanced supplement of calcium-magnesium – boron-zinc-manganese-(iron if deficient) and vitamins B, C, D and K. Since vitamin D intoxication (toxic rise in blood calcium- hypercalcemia) in some opinions requires ~>600 000iu/day for months, ths is inconceivable unless one were to swallow say twelve 50 000iu vitamin D every day for months. So the only recognized form of vitamin D intoxication could be an industrial accident involving mistaken use of vitamin D concentrate in medicine.

HYPERCALCEMIA HIGH BLOOD CALCIUM: medical causes are rare without gross calcium overdose (milk alkali syndrome) or other specific symptomatic diseases – eg primary hyperparathyroidism, sarcoidosis, tuberculosis, and lymphoma.And fortunately most patients with these diseases and hypercalcemia are far more likely to benefit from therapeutic treatment with vitamin D than worsen on it.

OVERDOSE: HYPERVITAMINOSIS D: WIKI says “Vitamin D stored in the human body as calcidiol (25-hydroxy-vitamin D) has a half-life of about 20 to 29 days.[17] Ordinarily, the synthesis of bioactive vitamin D hormone is tightly regulated, and prevalent thinking is that vitamin D toxicity usually occurs only if excessive doses (prescription forms or rodenticide[38] . Serum levels of calcidiol (25-hydroxy-vitamin D) are typically used to diagnose vitamin D overdose. In healthy individuals, calcidiol levels are normally between 32 to 70 ng/mL (80 to 175 nmol/L), but these levels may be as much as 15-fold greater in cases of vitamin D toxicity. Serum levels of bioactive vitamin D hormone (1,25(OH2)D) are usually normal in cases of vitamin D overdose. Symptoms include Dehydration Vomiting Decreased appetite (anorexia) Irritability Constipation Fatigue.

Overdose of vit D3 has been observed at 1925 µg/d (77,000 IU per day). Acute overdose requires between 600,000 and 1,680,000 IU per day over a period of several days to months, with a safe intake level being 10,000 IU per day.

A 2007 risk assessment suggested that 250 micrograms/day (10,000 IU) in healthy adults should be adopted as the tolerable upper limit.[39]In adults, sustained intake of 100,000 IU can produce toxicity within a few months.[2]For infants (birth to 12 months) the tolerable UL is set at 1000 IU, and 40,000 IU has been shown to produce toxicity within 1 to 4 months. All known cases of vitamin D toxicity with hypercalcemia have involved intake of or over 40,000 IU)[42].

Although normal food and pill vitamin D concentration levels are far too low to be toxic in adults, people taking multiples of the normal dose of codliver oil may reach toxic levels of vitamin A, not vitamin D, [43] if taken in an attempt to increase the levels of vitamin D. Most officially-recorded historical cases of vitamin D overdose have occurred due to manufacturing and industrial accidents.[42]

Some symptoms of vitamin D toxicity are a result of hypercalcemia caused by increased intestinal calcium absorption. Vitamin D toxicity is known to be a cause of high blood pressure.[45] Gastrointestinal symptoms of vitamin D toxicity can include anorexia, nausea, and vomiting. These symptoms are often followed by polyuria (excessive production of urine), polydipsia (increased thirst), weakness, nervousness, pruritus (itch), and eventually renal failure. Other signals of kidney disease including elevated protein levels in the urine, urinary casts, and a build up of wastes in the blood stream can also develop.[2] In one study, hypercalciuria and bone loss occurred in four patients with documented vitamin D toxicity.[46] Another study showed elevated risk of ischaemic heart disease when 25D was above 89 ng/mL.[47] Vitamin D toxicity is treated by discontinuing vitamin D supplementation, and restricting calcium intake. If the toxicity is severe blood calcium levels can be further reduced with corticosteroids or bisphosphonates. In some cases kidney damage may be irreversible.[2]

Exposure to sunlight for extended periods of time does not normally cause vitamin D toxicity.[42] This is because within about 20 minutes of ultraviolet exposure in light skinned individuals (3–6 times longer for pigmented skin) the concentration of vitamin D precursors produced in the skin reach an equilibrium, and any further vitamin D that is produced is degraded.[48]Maximum endogenous production with full body exposure to sunlight is 250 µg (10,000 IU) per day.[42]”

VITAMIN D AND SEX:

Biologically, the most imperative function for species survival is sex- reproduction. Vitamin D is clearly a potent anabolic reproductive steroid like testosterone: The first paper on this association on Pubmed appears in 1963 from Russia (Gokinaeva).

Mirzahossein in 1996 showed that,” given in the critical period of foetal imprinting, vitamin D may influence steroid hormone-receptor commanded events for life in a way similar to synthetic steroid hormone analogues”. So as with marine omega3., it is crucial that future parents take enough vitamin D.

Friedrich 2002 showed that even prostate, colon and normal cervical tissue and cervical cancer cells have VDRs – vit D receptors- and may be new targets for cancer prevention or cancer treatment.

VITAMIN D AND SLE- SYSTEMIC LUPUS ERYTHEMATOSIS: on medline the first reference to immunosuppression with vitamin D was by Bourdial 1963 on nasal allergy, and the first for vitamin D and immunomodulation is by Nagler & Pollack 1986.:

However, the first paper on the importance of Vitamin D3 deficiency in SLE appeared in Germany 1963, but the first paper in English and from an English country only in 1979 (O’Regan).

The focus throughout has been on the benefit of vitamin D in reversing the hyperimmunity of SLE, but of course vitamin D is equally important in preventing both the osteoporosis of inflammation, the fracture and wasting risks of cortisone treatment, and the vascular disease associated with SLE. In the last year alone there have been 10 such SLE – vitamin D major studies – 7 from the Americas and 3 from Europe.

SLE as well as plain lupus of the skin are generally regarded as disease that requires protection from the sun.

Now this week Wright 2009 shows that in children, SLE is associated with vitamin D deficiency, particularly among those subjects with SLE who are overweight.

VITAMIN D, SUNLIGHT, SLE AND CANCER:

The first case of SLE associated with cancer ( meningioma and cervix)- is reported by Williams 1956. The latest – last month- highlights increased risk of lymphoma, cervix and bronchus cancers.

Search for malignant melanoma MM and SLE finds the first reference in 1963. yet most of the papers are about reactions to interferon therapy, or immune markers- there is one solitary case report (1991 Sulkes, Israel) of a patient with indolent SLE who after 15 years developed and died of rapidly spread of MM. These authors comment on the infrequent association of SLE & solid cancers, the commonest being uterus and bladder.

So it is exciting that while more sun exposure causes skin cancer and especially cutaneous melanoma CMM, (Tuohimaa 2007), sun exposure also improves survival from CMM- and from a wide range of internal cancers – (especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder and kidney cancers). This favourable effect of more sunshine is obvious when comparing the lower cancer and heart disease deathrates in sunnier southern versus the darker northern countries. Only rare skin diseases eg porphyria cutanea tarda are contraindications to sun exposure of the skin. But at least one study Holme 2008 shows vitamin D deficiency in erythropoetic porphyria.

Professor Halstead 2008 (and many others) conclude that the high fructose corn syrup routinely used in fast foods and cooldrinks in first-world manufacturing is rapidly increasing obesity, lipidemia (and metabolic syndrome and cancer); while folic acid food fortification is causing low B12 levels and thus possibly increasing dementia, vascular disease and advanced precancerous colorectal adenomas and breast cancer. This trend is aggravated by at least three scientifically unvalidated obsessions of Regulators and the Medical hierarchy:

1. low diet cholesterol in those with mild to moderate cholesterolemia;

Protection from both cancers and SLE is probably associated with higher vitamin D level above ~100nmol/L. Both lupus and cancers are due to altered immunity. But SLE is due to increased autoimmunity- hence cancers are infrequent during active SLE; whereas cancers are due to reduced immunity – hence are associated with immune suppression, whether by cortisone (including stress) / chemotherapy, or deficiency of vitamin D – dietary and lack of sunshine..

While there is no clear overall relationship of statins to osteoporosis or cancer, Kunitomo 1989showed that cholesterol reduces and corticosteroids enhance the toxicity of vitamin D in rats. Montagnani 1994 showed that pravastain does not interfere with the circulating levels of the main vitamin D metabolites.

VITAMIN D AND INFECTION:

For an acute infection, Cannell and Hollis 2008 suggest vitamin D in an antimicrobial dose of 2000iu/kg eg 120 000 iu a day for 3 days- to produce enough of the naturally occuring antibiotic cathilicidin. Ginde 2009 show that those with high vitamin D levels have less respiratory infections. This column has previously reviewed the dramatic benefits of vitamin D on infection mortality in AIDs- TB patients. Obviously one is going to be cautious pushing vitamin D in a patient with known kidney stones, or hypercalcemia.

VITAMIN D : WHY THE INCREASING DEFICIENCY, NEED FOR SUPPLEMENT ?

Never mind the poor and chronically ill, the aging especially need much more vitamin D, and benefit the most. Even in a sunny fishing nation like Spain, elderly women do not get enough vitamin D from fish or other foods, and most have suboptimal blood levels of it.

Apart from dietary intolerance and obsession reducing intake of cholesterol and dairy products, the vitamins and minerals in particular have been greatly depleted and imbalanced in commercially produced- and especially genetically-modified food. And while increasing longevity, food scarcity -poverty and mushrooming prices (cartel pricefixing that is ignored by well-paid politicians and regulators) – are prime causes, Politicians and Regulators have worsened this by falling decades behind in ignoring the leading 20th pioneer nutritionist/ economists like the USA’s Professors Linus Pauling the unique double Nobel prizewinner prophet of vitamin C and peace; Ken Galbraith; and the UK’s SirJack Drummond. The latter two respectively brought the Allies (under FD Rooseveld and WS Churchill) through WW2 by putting farming- healthy food production and pricing- as the painfully obvious priority- which selfserving gluttonous politicians like Nixon, Bush, Kissinger, Mugabe and Mbeki, and most others leaders (who support, not just tolerate such despots) simply ignore since they detest “surplus people”- the honest poor; if not also hardworking farmers.

It is no coincidence that Pauling and Galbraith both graduated from agricultural colleges. And no coincidence that all three nutritionists were the targets of politician-business moguls because of the obstacles they posed to the profiteering national economic sabotage that is the lifeblood of ruthless businessmen-capitalists from before Nixon- Connolly- Reagan- Kissinger and Thatcher, through to the Bushes and Blair and Montsano-GD Searle, Mbeki and Zuma, and the arms, oil, banking, mining, media, food, sex, tobacco-alcohol and medical-big pharma industry mafiosi cartel who make or break presidents and governments.

James Ferguson makes a strong case for The Vitamin Murders, that Drummond (and his family) were butchered in a Vitamin Industry contract in France as a lesson to do-gooders because his advocacy of the primary role of good natural nutrition and vitamins was such an obstacle to the fast food and synthetic drug industry. Conspiracy theorists could argue that, like Pauling’s vitamin C, the Drug Industry have through the FDA managed to ensure that only this year is the FDA grudgingly moving to raise the Recommended daily Allowances of vitamin D (and C) even fractionally above the present rickets- (and scurvy) preventing doses, as opposed to their modest 25 to 50fold fold higher intakes that have been known already for decades to be both safe and major benefit against all diseases.

John Le Carre’s The Constant Gardner echoes that ongoing conspiracy scenario, the battle between Big Pharma with it’s drug lobbyists (including the USA FDA and the European Union’s European Medicine’s Authority, and leading politicians) to promote their lucrative modern synthetic chronic drugs (none of which have been shown to reduce all-cause disease and mortality as do natural supplements), versus nutritionists and informed consumers who know that broad natural supplements (vigorous vitamins, minerals and biologicals) to bolster the failing adulterated food chain are more important and effective than any patented designer drugs in combating all disease. Unfortunately the necessary advocacy for natural supplements has been muddied by fraudsters like the Big Pharma- FDA- academia cartel (who swamp the medical literature with trial and review papers favouring their snake oils), the Rath Foundation, and our local dissidents against reason like Mbeki, and Drs Manto Tshabalala-Msimang, Nkosasama Zuma and Olive Shishana.

CONCLUSION: In 2006 Dr Walter Stumpf in THE DOSE MAKES THE MEDICINE wrote: “in recent years, discussion raged about the negative effects of estrogen-replacement therapy and its relationship to cancer. In numerous articles, the side-effects of estrogen treatment were highlighted in a generalized fashion and, although consideration was given to the duration of treatment, the relationships to dose (let alone type and route of estrogen) were frequently left out. And yet, considerations of dose and time in pharmacology and toxicology are paramount.
Similarly, awareness of proper dosage is crucial to the development of future vitamin D therapies. Physiologic dosing of vitamin D does not cause hypercalcemia – hypercalcemia is related to overdosing ie closer to 100 000iu/day. Considering the many target tissues that are unrelated to systemic calcium regulation, most therapeutic effects of vitamin D occur independently of the high-dose systemic calcium effects. Because of the biased focus on calcium, the many other effects tend to remain unnoticed and hidden. Future research needs to give more consideration to dose-effect relationships by monitoring target functions independently of systemic calcium regulation.
New therapeutic applications of vitamin D can be established for cardiovascular, neurological, endocrine, immune, gastrointestinal, reproductive and other diseases, including posttraumatic and gerontological deficiencies, in which the polyfunctional effects of the hormone not only come to bear, but can also be controlled and maximized for optimal health.”

Since the global population shift from rural to city life and work the past century ie in our lifetispan, humans have largely gone from being healthy longlived outdoor food-producing workers living on their own fresh produce including organically grown unadulterated fresh food and dairy products – or fish- (rich in micronutrients), to working mostly indoors and consuming largely micronutrient-depleted food as well as multiple noxious deliberate industrial pollutants- from sugar and alcohol to estrogenics, pesticides, heavy metals, cornsyrup and aspartamate.

Like fish oil is the most important food extract we have (and businessmen are ruthlessly harvesting to extinction), vitamin D3 has become the anti-disease vitamin of the past decade, joining vitamins C & B as the panacea vitamins that can and should be supplemented in far higher dose than anti-vitamin “Regulators” and professional researchers and associations (with vested interests in protecting their funder- Big Pharma) approve.

But as the more affluent age and increase in numbers, the micronutrients that deplete (with longevity, the deteriorating food chain, and unnecessary drugs),- especially vitamins K, chondroglucosamine, N-acetyl cysteine, alphalipoic acid, Co-Q10, arginine, carnitine, carnosine, riboseand the marine EPA and DHA- are fast becoming the “vitamins” of the next decade.

Tragically, edible marine products especially marine omega3 EPA+DHA are rapidly becoming so scarce that the vast majority of people can neither source nor afford the minimum optimal gram a day, until science breaks through to synthesize these uniquely beneficial free fatty acids. But at least the supply of minerals, and vitamins including D3, is inexhaustible and therefore freely available at reasonable cost.

ndb

dedicated to Dr Walter Stumpf, whose >300 papers (~24% on vitamin D) on Medline apparently span 1963 to 2008- on vitamin D the first in 1979, the last 30years later appropriately on Vitamin D and the digestive system. By comparison, Pubmed lists only 3 papers by Albright, in 1938-9.